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1.
Acta Physiologica Sinica ; (6): 527-536, 2019.
Article in Chinese | WPRIM | ID: wpr-777159

ABSTRACT

The aim of this study was to investigate whether G protein-coupled estrogen receptor (GPER) could alleviate hippocampal neuron injury under cerebral ischemia-reperfusion injury (CIRI) by acting on endoplasmic reticulum stress (ERS). The CIRI animal model was established by middle cerebral artery occlusion (MCAO). Female ovariectomized (OVX) Sprague-Dawley (SD) female rats were randomly divided into 4 groups: control, ischemia-reperfusion injury (MCAO), vehicle (MCAO+DMSO), and GPER-specific agonist G1 (MCAO+G1) groups. The neurobehavioral score was assessed by the Longa score method, the morphological changes of the neurons were observed by the Nissl staining, the cerebral infarction was detected by the TTC staining, and the neural apoptosis in the hippocampal CA1 region was detected by TUNEL staining. The distribution and expression of GRP78 (78 kDa glucose-regulated protein 78) in the hippocampal CA1 region were observed by immunofluorescent staining. The protein expression levels of GRP78, Caspase-12, CHOP and Caspase-3 were detected by Western blot, and the mRNA expression levels of GRP78, Caspase-12, and CHOP were detected by the real-time PCR. The results showed that the neurobehavioral score, cerebral infarct volume, cellular apoptosis index, as well as GRP78, Caspase-12 and CHOP protein and mRNA expression levels in the MCAO group were significantly higher than those of control group. And G1 reversed the above-mentioned changes in the MCAO+G1 group. These results suggest that the activation of GPER can decrease the apoptosis of hippocampal neurons and relieve CIRI, and its mechanism may involve the inhibition of ERS.


Subject(s)
Animals , Apoptosis , Brain Ischemia , CA1 Region, Hippocampal , Cell Biology , Caspase 12 , Metabolism , Caspase 3 , Metabolism , Endoplasmic Reticulum Stress , Female , Heat-Shock Proteins , Metabolism , Neurons , Cell Biology , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Estrogen , Physiology , Receptors, G-Protein-Coupled , Reperfusion Injury , Transcription Factor CHOP , Metabolism
2.
Article in English | WPRIM | ID: wpr-717218

ABSTRACT

BACKGROUND: Puromycin aminonucleoside (PAN) is a known podocytotoxin. PAN-induced nephrosis is a widely used animal model for studying human idiopathic nephrotic syndrome. Abnormal protein accumulation associated with podocyte-specific endoplasmic reticulum (ER) stress damages cells structurally and functionally, which in turn induces apoptosis and severe proteinuria. In the present study, we investigated the effect of PAN on ER stress and apoptosis in podocytes in vitro. METHODS: Mouse podocytes were cultured and treated with various concentrations of PAN. ER stress markers were then evaluated by western blotting, and apoptosis was evaluated by fluorescence-activated cell sorting (FACS) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: PAN treatment increased ER stress markers such as activating transcription factor (ATF) 6α and caspase-12 in a dose-dependent manner at 12 and 24 hours, respectively. These markers were reduced by chemical chaperones, such as sodium 4-phenylbutyric acid and tauroursodeoxycholic acid. PAN treatment also increased 78 kD glucose-regulated protein (GRP78)/binding immunoglobulin protein (BiP) at the earlier stage of 12 hours. PAN significantly induced podocyte apoptosis in concentration- and time-dependent manners, as seen using FACS and TUNEL assays. This result was improved by Nox4 siRNA, ATF6 siRNA, and chemical chaperones. LY294002, a PI3-kinase inhibitor, significantly boosted ER stress and apoptosis. PAN-induced ER stress increased oxidative stress and subsequently induced apoptosis, and could be mitigated by inhibition of PI3-kinase signaling. CONCLUSION: Our findings suggest that PAN induces ER stress in podocytes mainly through the GRP78/BiP, ATF6α, and caspase-12 pathways, which trigger apoptosis via induction of oxidative stress. This stress is mitigated by inhibiting PI3-kinase signaling.


Subject(s)
Animals , Apoptosis , Blotting, Western , Caspase 12 , DNA Nucleotidylexotransferase , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Flow Cytometry , Humans , Immunoglobulins , In Situ Nick-End Labeling , In Vitro Techniques , Mice , Models, Animal , Nephrosis , Nephrotic Syndrome , Oxidative Stress , Phosphatidylinositol 3-Kinases , Podocytes , Proteinuria , Puromycin Aminonucleoside , Puromycin , RNA, Small Interfering , Sodium , Transcription Factors
3.
Article in Chinese | WPRIM | ID: wpr-773812

ABSTRACT

OBJECTIVE@#To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice.@*METHODS@#Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot.@*RESULTS@#Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA.@*CONCLUSIONS@#The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.


Subject(s)
Animals , Apoptosis , Caspase 12 , Caspase 3 , Metabolism , Creatine Kinase, MB Form , Blood , Endoplasmic Reticulum Stress , Heart Injuries , Heat-Shock Proteins , Metabolism , L-Lactate Dehydrogenase , Blood , Lung , Pathology , MAP Kinase Kinase 4 , Metabolism , Male , Mice , Mice, Inbred C57BL , Myocardium , Pathology , Random Allocation , Reperfusion Injury , Transcription Factor CHOP , Metabolism
4.
Article in Chinese | WPRIM | ID: wpr-771695

ABSTRACT

To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS), the male SD rats were intraperitoneally injected with streptozotocin(STZ, 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR), the low-dose Nar group(Nar25), the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25, Nar50, Nar100 groups were orally administered with Nar at the doses of 25.0, 50.0, 100.0 mg·kg⁻¹ per day, respectively, while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment, fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results, compared with control group, the myocardial structure was damaged, the content of MDA was increased, while the activities of SOD were decreased(<0.05) in T1DR group. GRP78, CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(<0.05, <0.01). Compared with T1DR group, myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased, while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(<0.05, <0.01). After treatment with Nar for 8 weeks, myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased, while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(<0.05, <0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.


Subject(s)
Animals , Apoptosis , Cardiotonic Agents , Pharmacology , Caspase 12 , Metabolism , Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Drug Therapy , Endoplasmic Reticulum Stress , Flavanones , Pharmacology , Heat-Shock Proteins , Metabolism , Male , Malondialdehyde , Metabolism , Oxidative Stress , Rats , Rats, Sprague-Dawley , Superoxide Dismutase , Metabolism , Transcription Factor CHOP , Metabolism
5.
Article in Chinese | WPRIM | ID: wpr-254968

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of hydrogen sulfide (H₂S) on oxidative stress and endoplasmic reticulum stress (ERS) in a rat model of diabetic cardiomyopathy (DCM).</p><p><b>METHODS</b>Thirty male SD rats were randomly divided into control group, diabetes group and treatment group( n = 10). Intraperitoneal injection of streptozotocin was utilized to establish a rat model of DCM. The rats with DCM in treatment group were intraperitoneally injected with NaHS solution. After treated for 12 weeks, the hearts isolated from rats were perfused on a langendorff apparatus. The ventricular hemodynamic parameters were measured. The ultrastructures of myocardium were observed using electron microscopy. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in myocardial tissue were determined by spectrophotometry. The expressions of C/EBP homologous protein( CHOP), glucose-regulated protein 78 (GRP78) and Caspase 12 at mRNA level in myocardium were detected using RT-PCR.</p><p><b>RESULTS</b>Compared with control group, the cardiac function and myocardial ultrastructure were damaged obviously in diabetic rats. In myocardial tissue, the content of MDA was increased, while the activities of SOD and GSH-Px were decreased. CHOP, GRP78 and Caspase 12 mRNA expressions were increased significantly. Compared with diabetes group, cardiac function and myocardial ultrastructure damage were improved in treatment group. The content of MDA was decreased, while the activities of SOD and GSH-Px were increased significantly. The mRNA levels of CHOP, GRP78 and Caspase 12 were increased.</p><p><b>CONCLUSION</b>H2S can protect myocardium in diabetic rats, maybe it is related to reduce oxidative stress damage and inhibition of the ERS-induced apoptosis pathway.</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Diabetic Cardiomyopathies , Drug Therapy , Endoplasmic Reticulum Stress , Glutathione Peroxidase , Metabolism , Heat-Shock Proteins , Metabolism , Hydrogen Sulfide , Pharmacology , Male , Malondialdehyde , Metabolism , Myocardium , Oxidative Stress , Rats , Streptozocin , Superoxide Dismutase , Metabolism , Transcription Factor CHOP , Metabolism
6.
Chinese Medical Journal ; (24): 2845-2852, 2016.
Article in English | WPRIM | ID: wpr-230869

ABSTRACT

<p><b>BACKGROUND</b>Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.</p><p><b>METHODS</b>The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.</p><p><b>RESULTS</b>Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes.</p><p><b>CONCLUSIONS</b>These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.</p>


Subject(s)
Alzheimer Disease , Metabolism , Amyloid beta-Peptides , Metabolism , Animals , Apoptosis , Physiology , Blotting, Western , Caspase 12 , Metabolism , Endoplasmic Reticulum Stress , Physiology , Frontal Lobe , Metabolism , Heat-Shock Proteins , Metabolism , Immunohistochemistry , Mice , Mice, Transgenic , Neurons , Metabolism , Transcription Factor CHOP , Metabolism , Ubiquitin-Protein Ligases , Metabolism , Unfolded Protein Response , Physiology
7.
Acta Physiologica Sinica ; (6): 733-739, 2016.
Article in Chinese | WPRIM | ID: wpr-331609

ABSTRACT

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.


Subject(s)
Animals , Apoptosis , Caspase 12 , Cell Line, Tumor , Cell Survival , Endoplasmic Reticulum Stress , Macrophages , Mice , Phenylbutyrates , Serum Albumin , Tunicamycin
8.
Article in Chinese | WPRIM | ID: wpr-328236

ABSTRACT

<p><b>OBJECTIVE</b>To observe the protective effects of Tongxinluo (TXL) on apoptosis of rat cardiac microvascular endothelial cells (RCMECs) resulting from homocysteine (Hcy) induced endoplasmic reticulum stress (ERS), and to determine the signaling pathway behind its protection.</p><p><b>METHODS</b>Primary cultured RCMECs were isolated from neonatal rats using tissue explant method. The morphology of RCMECs was observed using inverted microscope, identified and differentiated by CD31 immunofluorescence method. Selected were well growing 2nd-4th generations of RCMECs. The optimal action time was determined by detecting the expression of glucose regulated protein 78 (GRP78) using immunofluorescence method. In the next experiment RCMECs were divided into 5 groups, i.e., the blank control group, the Hcy induced group (Hcy 10 mmol/L, 10 h), the Hcy + TXL group (Hcy 10 mmol/L + TXL 400 µg/mL), the Hcy +LY294002 group (Hcy 10 mmol/L + LY294002 5 µmol/L, LY294002 as the inhibitor of PI3K), the Hcy + LY294002 + TXL group (Hcy 10 mmol/L + LY294002 5 µmol/L + TXL 400 µg/mL). The apoptosis rate of RCMECs was detected by flow cytometry. mRNA and protein expressions of GRP78, C/ EBP homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase12) were detected by real-time reverse transcription PCR (RT-PCR) and Western blot respectively. Expression levels of phosphorylation of phosphatidylinositol 3-kinase (P-PI3K), total phosphatidylinositol 3-kinase (T- P13K) , phosphorylation of kinase B (P-Akt) , and total kinase B (T-Akt) were detected by Western blot.</p><p><b>RESULTS</b>Ten hours Hcy action time was determined. Compared with the blank control group, the apoptosis rate was increased (22.77%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, protein expressions of P-PI3K and P-Akt,ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy induced group (P < 0.05, P < 0.01). Compared with the Hcy induced group, the apoptosis rate was decreased (10.17%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were decreased, and expression levels of P-PI3K, P-Akt, P-PI3K/T-PI3K, and P-Akt/T-Akt were increased in the Hcy + TXL group (P < 0.05, P < 0.01). Compared with the Hcy + TXL group, the apoptosis rate was increased (17.9%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, expression levels of P-PI3K and P-Akt, ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy + TXL + LY294002 group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>TXL could inhibit the apoptosis of RCMECs resulting from Hcy-induced ERS and its mechanism might be associated with activating PI3K/Akt signaling pathway.</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Cells, Cultured , Chromones , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Endoplasmic Reticulum Stress , Endothelial Cells , Morpholines , Pharmacology , Myocardium , Cell Biology , Phosphatidylinositol 3-Kinases , Metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Rats , Signal Transduction , Transcription Factor CHOP , Metabolism
9.
Article in Chinese | WPRIM | ID: wpr-815359

ABSTRACT

OBJECTIVE@#To explore the mechanism of tauroursodeoxycholic acid (TUDCA) in suppressing apoptosis in pulmonary tissues of intermittent hypoxia (IH) mice model.
@*METHODS@#A total of 32 C57 mice were randomly divided into a control group, a TUDCA group, an IH group and an IH+TUDCA group (8 mice per group). The mice were put in specially designed chambers and exposed to IH treatment for 4 weeks. In the chambers, oxygen levels repeatedly decreased from 21% to 10% and recovered from 10% to 21%, lasting for 8 hours in every day. After 4 weeks of IH exposure, the expression levels of caspase-12 and cleaved caspase-3 in pulmonary tissues were detected by Western blot. Meanwhile, the expression levels of glucose regulated protein-78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were quantified by Western blot, immunochemistry and real-time PCR.
@*RESULTS@#Compared with the control group, the expression levels of caspase-12, cleaved caspase-3, GRP78 and CHOP were increased in the IH group (all P<0.01). TUDCA treatment could reduce these proteins expression (all P<0.05).
@*CONCLUSION@#Endoplasmic reticulum stress-mediated apoptosis can be activated in pulmonary tissues after chronic IH exposure, and TUDCA can reduce the cellular apoptosis via suppressing endoplasmic reticulum stress.


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Caspase 3 , Metabolism , Disease Models, Animal , Endoplasmic Reticulum Stress , Heat-Shock Proteins , Metabolism , Hypoxia , Lung , Mice , Mice, Inbred C57BL , Real-Time Polymerase Chain Reaction , Taurochenodeoxycholic Acid , Pharmacology , Transcription Factor CHOP , Metabolism
10.
National Journal of Andrology ; (12): 402-407, 2015.
Article in Chinese | WPRIM | ID: wpr-276085

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of endoplasmic reticulum stress in the apoptosis of testicular germ cells in hyperlipidemic rats.</p><p><b>METHODS</b>We randomly assigned 42 four-week-old male Wistar rats into a normal control group (n = 12) and a high-fat group (n = 30) to be fed on a normal diet and a high-fat diet, respectively, for 10 weeks. Then we measured the concentrations of triglyceride (TG) and total cholesterol (TC) in the serum using an automatic biochemistry analyzer, detected the apoptosis of testicular germ cells by TUNEL staining, and determined the protein and mRNA expressions of GRP78 and. caspase-12 in the testis tissue by immunohistochemistry and RT-PCR, respectively.</p><p><b>RESULTS</b>The concentrations of TG and TC were significantly increased in the animals of the high-fat group ([3.00 ± 0.92] and [3.04 ± 0.39] mmol/L) as compared with the control rats ([1.43 ± 0.41] and [1.55 ± 0.23] mmol/L) (P < 0.01), and so was the apoptosis index of the testicular germ cells ([37.17 ± 2.74]% vs [5.16 ± 0.81]%, P < 0.01). The high-fat group, in comparison with the control, also showed remarkably upregulated protein and mRNA expressions of GRP78 (0.32 ± 0.03 and 0.86 ± 0.05 vs 0.19 ± 0.01 and 0.37 ± 0.03, P < 0.01) and caspase-12 (0.34 ± 0.02 and 0.87 ± 0.01 vs 0.12 ± 0.01 and 0.34 ± 0.03, P < 0.01) in the testis tissue.</p><p><b>CONCLUSION</b>The apoptosis of testicular germ cells is increased in hyperlipidemic rats, which may be attributed to endoplasmic reticulum stress.</p>


Subject(s)
Animals , Apoptosis , Physiology , Caspase 12 , Metabolism , Cholesterol , Blood , Diet, High-Fat , Endoplasmic Reticulum Stress , Physiology , Heat-Shock Proteins , Metabolism , In Situ Nick-End Labeling , Male , Random Allocation , Rats , Rats, Wistar , Spermatozoa , Pathology , Staining and Labeling , Testis , Metabolism , Transcriptional Activation , Triglycerides , Blood , Up-Regulation
11.
Article in Chinese | WPRIM | ID: wpr-255005

ABSTRACT

<p><b>OBJECTIVE</b>To observe the the expression of endoplasmic reticulum stress (ERS) related factors in deep tissue injury (DTI) at pressure ulcer rat and to investigate the ERS mechanism of DTI in muscle tissue and protective effect of 4-phenylbutyric acid (4-PBA) in local tissue.</p><p><b>METHODS</b>Fifty male SD rats were randomly devided into control group, model group, experimental group NS group and PBA group, the experimental groups were divided into 4 d, 7 d, 14 d and 21 d group according to the observation time (n = 5). Rats in the PBA group were administrated with gastric perfusion of 4-PBA after the modeling; the NS group was given normal saline of the same quantity. Using HE staining to observe morphologic character. The expression of glucose regulated protein 78 (GRP78), CHOP, Caspase 12 were detected by immunohistochernical staining. Cell apoptosis was detected by TUNEL assay.</p><p><b>RESULTS</b>HE staining results showed that each group demonstrated compression injury compared with control group: cellular swelling, ompaction of nuclear, and apoptosis in muscle tissue. The new muscle fiber in 4-PBA group fused faster than those in NS group. The number of TUNEL positive cells peaked at 4 day after compression, then got decreased on day 7 in muscle tissue, apoptosis positive cells were diminished after 4-PBA treatment. The immunohistochemical staining results showed that the expression of protein GRP78, CHOP, Caspase 12 peakd 4 d after modeling and decreased gradually. The GRP78, CHOP, Caspase 12 protein expression were significantly higher than those of PBA group at all time points (P < 0.05).</p><p><b>CONCLUSION</b>Cell apoptosis induced by endoplasmic reticulum stress took part in deep tissue injury resulting of pressure ulcer, which mechanism might be related to reducing apoptosis mediated by CHOP, Caspase 12.</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Endoplasmic Reticulum Stress , Heat-Shock Proteins , Metabolism , Male , Muscle, Skeletal , Pathology , Phenylbutyrates , Pharmacology , Pressure Ulcer , Proteomics , Rats , Rats, Sprague-Dawley , Transcription Factor CHOP , Metabolism
12.
Chinese Medical Journal ; (24): 1523-1528, 2015.
Article in English | WPRIM | ID: wpr-231744

ABSTRACT

<p><b>BACKGROUND</b>Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats. In this study, we observed the effect of salubrinal (Sal, Sigma, USA) on liver cells in BD rats and explored its relevant mechanisms.</p><p><b>METHODS</b>Thirty Sprague-Dawley rats were equally randomized into three groups: BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered 1 h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase (PERK), P-eukaryotic translation initiation factor 2α (eIF2α), eIF2α, CHOP and caspase-12 expression was detected using western blotting (WB). CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC). Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software (Bio-Rad, USA).</p><p><b>RESULTS</b>CHOP and caspase-12 expression and PERK, eIF2α, and P-eIF2α protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05). However, eIF2α expression showed no significant difference (P > 0.05). After the Sal treatment, CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05). WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis.</p><p><b>CONCLUSIONS</b>Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-eIF2α signaling pathway.</p>


Subject(s)
Animals , Apoptosis , Blotting, Western , Brain Death , Metabolism , Caspase 12 , Genetics , Metabolism , Cinnamates , Disease Models, Animal , Endoplasmic Reticulum Stress , Eukaryotic Initiation Factor-2 , Genetics , Metabolism , Immunohistochemistry , Liver , Wounds and Injuries , Male , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Thiourea , Transcription Factor CHOP , Genetics , Metabolism
13.
Article in Chinese | WPRIM | ID: wpr-356979

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of adenosine preconditioning on cell apoptosis and expressions of glucose-regulated protein (GRP-78) and cysteinyl aspartate-specific protease 12 (caspase-12) in rats with spinal cord ischemia-reperfusion injury.</p><p><b>METHODS</b>Twenty-seven rats were randomized into 3 equal groups and subjected to sham operation (group A), spinal cord ischemia-reperfusion injury (group B), or ischemia-reperfusion injury with adenosine treatment. Spinal cord ischemia-reperfusion injury was induced by cross-clamping of the abdominal aorta inferior to the left renal artery. The spinal cord function was assessed using the Modified Tarlov Scale at 6, 12, and 24 h after reperfusion. At 24 h after reperfusion, histological analysis was carried out with HE staining; cell apoptosis and viability were determined with TUNEL staining, and the expressions of GRP-78 and caspase-12 proteins were determined with Western blotting.</p><p><b>RESULTS</b>HE staining of the spinal cord showed extensive spinal cord injury such as cell edema in group B as compared with group C. Compared with group A, group B showed a significantly increased number of apoptotic cells; the number of apoptotic cells in group B was greater than that in group C. Compared with group B, group C showed significantly increased GRP-78 expression (P<0.01) and decreased caspase-12 expression (P<0.01).</p><p><b>CONCLUSION</b>Adenosine can up-regulate GRP-78 expression and down-regulate caspase-12 expression, and protects the spinal cord against ischemia-reperfusion injury by inhibiting cell apoptosis.</p>


Subject(s)
Adenosine , Pharmacology , Animals , Apoptosis , Caspase 12 , Metabolism , Heat-Shock Proteins , Metabolism , Ischemic Preconditioning , Methods , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Metabolism , Spinal Cord Ischemia , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-306261

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of oxidative stress in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust.</p><p><b>METHODS</b>Seventy-two healthy adult Wistar rats were randomly divided into control group, quartz dust group, quartz dust plus N-acetyl cysteine (NAC) group, and NAC group, with 18 rats in each group. One milliliter of sterile saline (for the control and NAC groups) or 1 ml of saline with 5%ultrafine quartz dust (for dust group and dust plus NAC group) was given to each rat by non-exposed endotracheal infusion. From the second day after dust infusion, rats in dust plus NAC group and NAC group received intragastric administration of NAC (100 mg/kg). In each week, the treatment with NAC lasted for 5 consecutive days, followed by 2 days' interval. For each group, 6 rats were randomly selected on the 14th, 28th, or 56th day after dust exposure; they were sacrificed by bloodletting from the femoral artery, and the lungs were collected. Bronchoalveolar lavage fluid was collected to separate macrophages. The protein expression of caspase-12 in alveolar macrophages, the apoptosis rate and reactive oxygen species (ROS) content of alveolar macrophages, and the protein carbonyl content of alveolar macrophages were determined by Western blot, flow cytometry, and colorimetry, respectively.</p><p><b>RESULTS</b>Increased protein expression of caspase-12, apoptosis rate, and content of ROS and protein carbonyl were discovered on the 14th day in the dust group, in comparison with the control group (P < 0.05), and the increase lasted till the 28th and 56th days. (P < 0.05). Compared with the dust group, the dust plus NAC group showed significant decreases in the content of ROS on the 14th, 28th, and 56th days (P < 0.05), significant decreases in the content of protein carbonyl on the 28th and 56th days (P < 0.05), and significant decreases in the protein expression of caspase-12 and apoptosis rate (P < 0.05).</p><p><b>CONCLUSION</b>Oxidative stress is potentially involved in the endoplasmic reticulum stress-induced apoptosis of alveolar macrophages triggered by quartz dust. Oxidative damage of protein in the endoplasmic reticulum may play an important role in the process.</p>


Subject(s)
Animals , Caspase 12 , Metabolism , Dust , Endoplasmic Reticulum Stress , Macrophages, Alveolar , Pathology , Male , Oxidative Stress , Protein Carbonylation , Quartz , Toxicity , Rats , Rats, Wistar , Reactive Oxygen Species , Metabolism
15.
Article in Chinese | WPRIM | ID: wpr-294336

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effect of curcumin (CUR) on cycteinyl aspirate specific protease-12 (Caspase-12) and pneumocyte apoptosis in pulmonary ischemia/reperfusion (I/R) injury mice.</p><p><b>METHODS</b>The in vivo unilateral in situ pulmonary I/R injury mouse model was established in C57BL/6J mice. Sixty experimental mice were randomly divided into six groups by random digit table, i. e., the sham-operation group (Sham), the I/R group, the I/R + dimethyl sulfoxide group (I/R + DMSO), the I/R + low dose CUR pre-treated group (I/R + CUR-100), the I/R + middle dose CUR pre-treated group (I/R + CUR-150), the I/R + high dose CUR pre-treated group (I/R + CUR-200), 10 in each group. Mice were euthanized and their left lungs were excised. Wet lung weight to dry lung weight (W/D) and the total lung water content (TLW) were tested. The morphological changes of the lung tissue were observed and index of quantitative evaluation for alveolar damage (IQA) detected under light microscope. The ultra-microstructure of the lung tissue was observed under electron microscope. The mRNA and protein expression levels of Caspase-12 and glucose regulated protein (GRP78) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Apoptosis index (AI) of the lung tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method.</p><p><b>RESULTS</b>Compared with the Sham group, expression levels of Caspase-12, GRP78 mRNA and protein all significantly increased in the I/R group (P < 0.05); W/D, TLW, IQA, and AI were all notably higher (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were notably observed in I/R group. Compared with the I/R + DMSO group, expression levels of GRP78 mRNA and protein were increasingly higher in the I/R + CUR-100 group, the I/R + CUR-150 group, and the I/R +CUR-200 group (P < 0.05), expression levels of Caspase-12 mRNA and protein were lower (P < 0.05); W/D, TLW, IQA, and AI also decreased (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were gradually alleviated in the I/R + CUR groups.</p><p><b>CONCLUSION</b>CUR had better effect on the lung protection against I/R injury, which might be related to inhibition for pneumocyte apoptosis associated with Caspase-12 in excessive unfolded protein response (UPR).</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Curcumin , Pharmacology , Heat-Shock Proteins , Metabolism , Lung , Male , Mice , Mice, Inbred C57BL , Reperfusion Injury , Metabolism , Pathology
16.
Chinese Medical Journal ; (24): 4517-4523, 2013.
Article in English | WPRIM | ID: wpr-327538

ABSTRACT

<p><b>BACKGROUND</b>Accumulated evidence shows that hypoxia can induce endothelial apoptosis, however the mechanism is still unknown. We hypothesized whether intermittent or persistent hypoxia could induce endoplasmic reticular stress, leading to endothelial apoptosis.</p><p><b>METHODS</b>Twenty-four 8-week male Sprague Dawley (SD) rats were divided into three groups: normoxia (NC) group, intermittent hypoxia (IH) group and persistent hypoxia (PH) group. TUNEL staining was performed to detect aortic arch endotheliar apoptosis, and immunohistochemistry for BIP, CHOP and caspase12 to test protein expression; human umbilical vein endothelial cells (HUVECs) of the line ECV304 were cultured (with or without taurodeoxycholic acid (TUDCA) 10 mmol/L, 100 mmol/L) and divided into four groups: NC group (20.8% O2 for 4 hours), PH1 group (5% O2 for 4 hours), PH2 group (5% O2 for 12 hours) and IH group (20.8% O2 and 5% O2 alternatively for 8 hours). Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis in each group. The expressions of GRP78, CHOP and caspase12 were detected by real-time quantitative reverse-transcription PCR. Result Intermittent and persistent hypoxia could increase the rate of endothelium apoptosis and the expressions of GRP78, CHOP and caspase12 compared with the control, induction by intermittent hypoxia was slightly higher than persistent hypoxia. In the HUVEC experiment, TUDCA significantly reduced apoptosis and the expressions of GRP78, CHOP and caspase12.</p><p><b>CONCLUSION</b>Hypoxia, especially intermittent, can induce endothelial cell apoptosis possibly through endoplasmic reticulum stress pathway, which can be attenuated by taurodeoxycholic acid.</p>


Subject(s)
Animals , Apoptosis , Genetics , Physiology , Caspase 12 , Genetics , Endoplasmic Reticulum Stress , Genetics , Physiology , Heat-Shock Proteins , Genetics , Human Umbilical Vein Endothelial Cells , Humans , Hypoxia , Genetics , Male , Rats , Rats, Sprague-Dawley , Taurodeoxycholic Acid , Pharmacology , Transcription Factor CHOP , Genetics
17.
Chinese Journal of Pathology ; (12): 112-118, 2012.
Article in Chinese | WPRIM | ID: wpr-241983

ABSTRACT

<p><b>OBJECTIVE</b>To clarify the effects of endoplasmic reticulum stress (ER stress) and mitogen-activated protein kinase (MAPK) on hepatocyte apoptosis in rats with non-alcoholic fatty liver fibrosis induced by methionine-choline-deficient diet (MCDD).</p><p><b>METHODS</b>Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by giving a MCDD for 10 weeks (group M). A methionine-choline-control diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental group (group R). Steatosis, fibrosis and inflammation were determined by tissue staining. The activation of hepatic stellate cells and oxidative stress were determined by immunostaining, immunoblotting or real time-PCR (RT-PCR), respectively. Hepatocyte apoptosis was determined by TUNEL staining. Expressions of glucose-regulated protein 78 (GRP78), caspase-12, caspase-7, cleaved caspase-7, caspase-3, cleaved caspase-3, and caspase-9 were evaluated to clarify the presence of ER stress. Expressions of c-Jun, ERK1/2, p-ERK1/2 were evaluated to clarify the states of MAPK signaling.</p><p><b>RESULTS</b>Changing the diet from MCDD to MCCD triggered the reduction of fat in hepatocytes, a decrease in inflammatory response, oxidative stress, and fibrosis. The protein expressions of ERP78, caspase-12, caspase-7, and cleaved caspase-7 were increased significantly in group M compared with normal control group (group N, P < 0.05 or P < 0.01), the mRNA expressions of ERP78, caspase-12, and caspase-7 were also increased significantly in group M compared with group N (3.03 ± 0.41 vs 2.12 ± 0.37, 1.86 ± 0.36 vs 0.78 ± 0.20, and 2.38 ± 0.19 vs 1.84 ± 0.13, respectively, P < 0.05 or P < 0.01), while they recovered immediately in group R. In contrast, the protein levels of caspase-3, cleaved caspase-3 and mRNA expressions of caspase-3 and caspase-9 revealed no significant differences in three groups (P > 0.05). The mRNA expressions of c-Jun and protein levels of ERK1 and p-ERK1 were increased significantly in group M compared with group N (P < 0.01), while they recovered immediately after changing the diet from MCDD to MCCD.</p><p><b>CONCLUSIONS</b>ER stress plays a role in the development and regression of non-alcoholic fatty liver fibrosis induced by MCDD, however, ER stress-related caspase-12 pathway may not be the main mechanism of hepatic apoptosis, and MAPK signaling may play an important role in hepatic apoptosis in the model.</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Caspase 3 , Metabolism , Caspase 7 , Metabolism , Caspase 9 , Metabolism , Choline Deficiency , Diet , Endoplasmic Reticulum Stress , Physiology , Fatty Liver , Metabolism , Pathology , Heat-Shock Proteins , Metabolism , Hepatocytes , Pathology , Liver Cirrhosis , Metabolism , Pathology , Male , Methionine , Mitogen-Activated Protein Kinases , Metabolism , Non-alcoholic Fatty Liver Disease , Proto-Oncogene Proteins c-jun , Metabolism , RNA, Messenger , Metabolism , Rats , Rats, Wistar , Signal Transduction
18.
Article in Chinese | WPRIM | ID: wpr-298999

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of berberine on the pancreatic 13 cell apoptosis in rats with insulin resistance (IR).</p><p><b>METHODS</b>IR Wistar rat model was established by feeding with high fructose diet. After 6-week treatment of berberine, oral glucose tolerance test (OGTT) was performed. Then fasting insulin level (Fins) was detected and insulin sensitivity index (ISI) calculated. The islet was isolated and purified. The pancreatic p3 cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The apoptosis-related protein ASK1 and Caspase-12 expressions were examined by immunohistochemical assay.</p><p><b>RESULTS</b>Compared with the normal group, the blood glucose at 0 and 1 h increased, the Fins increased and ISI decreased, the blood lipids were disarranged, the pancreatic beta cell apoptosis increased, and ASK1 and Caspase-12 protein expressions increased in IR rats. Compared with the model group, the blood glucose at 0 and 1 h and the Fins decreased, ISI increased, the disarranged blood lipids were improved, the pancreatic beta cell apoptosis decreased, and the ASK1 expression decreased, but with no obvious change in the Caspase-12 expressions in the berberine group.</p><p><b>CONCLUSIONS</b>Berberine could alleviate IR state in IR rats and inhibit pancreatic 13 cell apoptosis. Its mechanism might be correlated with the inhibition of ASK1 protein expressions.</p>


Subject(s)
Animals , Apoptosis , Berberine , Pharmacology , Blood Glucose , Caspase 12 , Metabolism , Cell Line , Insulin Resistance , Insulin-Secreting Cells , Cell Biology , MAP Kinase Kinase Kinase 5 , Metabolism , Male , Rats , Rats, Wistar
19.
Chinese Journal of Pediatrics ; (12): 53-59, 2011.
Article in Chinese | WPRIM | ID: wpr-286143

ABSTRACT

<p><b>OBJECTIVE</b>To observe the expression of GRP78 (glucose regulated protein, GRP78), Caspase-12 and the change of neuron apoptosis in the juvenile rat hippocampus after status convulsive (SC), and to explore the effect of edaravone on them.</p><p><b>METHODS</b>One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into normal saline control group (NS group), status convulsive group (SC group) and edaravone treatment group (ED group). Each group was further divided into five subgroups in different executed time points after SC. The rats in status convulsive group were kindled into epilepsy by lithium-pilocarpine method. Expression of GRP78 mRNA and caspase-12 mRNA was detected with reverse transcription-polymerase chain reaction (RT-PCR) method. Expressions of GRP78 and caspase-12 protein were detected with immunohistochemical methods. The neuron apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL).</p><p><b>RESULTS</b>(1) Measured by immunohistochemistry the value of OD of GRP78 (0.1480 ± 0.0164, 0.1682 ± 0.0114, and 0.1540 ± 0.0102, respectively, 12 h - 48 h points) and caspase-12 (0.1325 ± 0.0165, 0.1794 ± 0.0213, 0.1525 ± 0.0423, and 0.1309 ± 0.0199, respectively, 12 h-72 h points) positive cells in the SC group increased, there was a significant difference compared with NS group (GRP78: 0.1214 ± 0.0147, 0.1272 ± 0.0177, and 0.1260 ± 0.0157, respectively, 12 h-72 h points. Caspase-12: 0.1050 ± 0.0121, 0.1041 ± 0.0151, 0.1058 ± 0.0222, and 0.1036 ± 0.0186, respectively, 12 h - 72 h points) (P < 0.01, or P < 0.05). By ED intervention GRP78 (0.1550 ± 0.0131, 0.1886 ± 0.0154, and 0.1721 ± 0.0151, respectively, 12 h - 48 h points) positive cells value of the OD increased as compared with SC group (P < 0.01, or P < 0.05). and caspase-12 (0.1211 ± 0.0184, 0.1545 ± 0.0205, and 0.1085 ± 0.0219, respectively, 12 h, 24 h and 72 h points) positive cells value of the A decreased as compared with SC group (P < 0.01, or P < 0.05). (2) Measured by RT-PCR, the expression of GRP78 mRNA and caspase-12 mRNA trend was similar to protein. (3) The TUNEL positive cells in hippocampus CA(1) of SC group (11.41 ± 2.37) were more than that of NS group after the SC 12 h (P < 0.01), reached its highest level at 48 h (28.78 ± 5.11), after the intervention with edaravone (8.98 ± 2.22, 13.09 ± 2.54 and 20.57 ± 4.89, respectively, 12 h-48 h points), TUNEL positive cells showed a significant drop in SC group at 12 h-48 h time points (P < 0.01, or P < 0.05), but still significantly higher than that of the NS group (6.22 ± 1.50, 6.57 ± 1.61 and 6.72 ± 1.14, respectively) (P < 0.01, or P < 0.05), at the 4 h time point (NS group 6.29 ± 1.49, SC group 6.61 ± 1.71, ED group 5.75 ± 1.41) among the three groups, no significant difference in TUNEL positive cells was found (P = 0.759).</p><p><b>CONCLUSIONS</b>The expression of GRP78 and caspase-12 increased after SC. Edaravone increased expression of GRP78 and decreased expression of caspase-12 in hippocampus rat with pilocarpine-induced seizures, reduced the number of neuronal apoptosis. These results suggest that edaravone may have protective effect against the hippocampal damage caused by status convulsive.</p>


Subject(s)
Animals , Antipyrine , Pharmacology , Apoptosis , Caspase 12 , Metabolism , Heat-Shock Proteins , Metabolism , Hippocampus , Metabolism , Male , Rats , Rats, Sprague-Dawley , Seizures , Metabolism
20.
Article in Chinese | WPRIM | ID: wpr-351189

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats.</p><p><b>METHODS</b>Uninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked.</p><p><b>RESULTS</b>Compared with those in normal control group, the numbers of apoptosis and the expression of GRP78, Caspase-12 in glomerular and tubular cells were much higher in the diabetic kidneys at 8 weeks. There was no significant difference between group A and group B.</p><p><b>CONCLUSION</b>Activation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.</p>


Subject(s)
Animals , Apoptosis , Caspase 12 , Metabolism , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Pathology , Endoplasmic Reticulum Stress , Heat-Shock Proteins , Metabolism , Kidney Cortex , Metabolism , Pathology , Male , Proliferating Cell Nuclear Antigen , Metabolism , Rats , Rats, Wistar
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