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【Objective】 To evaluate the effects of miR-148a-3p on calreticulin (CRT) expression and mitochondrial function in cardiomyocytes incubated with high glucose. 【Methods】 miR-148a-3p minic and inhibitor were used to intervene the H9c2 cardiomyocytes of rats. The expression of CRT protein was detected. Then the cells were divided into control group, high-glucose group (HG), HG +miR-148a-3p minic group, HG + miR-148a-3p minic + TG (CRT agonist) group, HG + miR-148a-3p inhibitor group, and HG + miR-148a-3p inhibitor + CRT- (CRT-siRNA) group. The content of adenosine triphosphate (ATP) and the level of reactive oxygen species (ROS), the activity of mitochondrial respiratory chain complex enzyme and apoptotic rate were detected. 【Results】 miR-148a-3p minic significantly inhibited the expression of CRT protein in cardiomyocytes, while miR-148a inhibitor increased the expression of CRT. miR-148a-3p minic inhibited the decrease of ATP production, the increase of ROS production and cell apoptosis, and the inactivity of mitochondrial respiratory chain complex enzyme in cardiomyocytes induced by high glucose, while TG weakened the above effects of miR-148a-3p minic. miR-148a inhibitor aggravated the mitochondrial injury and apoptosis of cardiomyocytes induced by high glucose, but the effects of miR-148a-3p inhibitor were partially blocked by CRT-siRNA. 【Conclusion】 miR-148a-3p negatively regulates the expression of CRT in cardiomyocytes and protects the mitochondrial injury and apoptosis induced by high-glucose through inhibiting CRT.
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Aim To investigate the protective effect and mechanism of JTE-013 on allergic rhinitis (AR) by regulating mitochondrial injury and apoptosis through RhoA/ROCKl/Drpl pathway. Methods AR model was established by ovalbumin (OVA) in mice. Nasal tissue sections were then stained with HE, TUNEL and DHE. Western blot assay. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with human recombinant interleukin-13 (IL-13), and the effects of JTE-013 and Y27632-related protein expression were detected by Western blot. Immunofluorescence was used to observe the effects of JTE-013 and Y 27632 on total ROS, mitochondrial membrane potential and mitochondrial ROS generation, Drpl translocation and Cyt-c expression in cells. Results JTE-013 reduced the frequency of nose rubbing and sneezing, reduced nasal mucosal thickening and decreased eosinophil infiltration in AR mice. TUNEL and DHE staining results suggested that JTE-013 could inhibit apoptosis and reduce ROS expression in mouse nasal epithelial cells. Western blot showed that both JTE-013 and Y 27632 could significantly reduce RhoA, ROCK1, Drpl and p-Drpl(616), inhibit the expression of apoptotic proteins Bax, cleaved-caspase-3, Cyt-c, cleavedcaspase-9 and up-regulate the expression of p-Drpl (637) and Bcl-2. Immunofluorescence showed that inhibitors of JTE-013 or ROCK1 almost blocked IL-13mediated increase in ROS and mtROS production, inhibited decrease in mitochondrial membrane potential, and blocked Cyt-c expression and Drpl translocation in nasal mucosal epithelial cells. Conclusion JTE-013 can regulate the morphology and function of mitochondria by inhibiting RhoA/ROCKl/Drpl signaling axis, thereby alleviating nasal epithelial cell inflammation in mice with allergic rhinitis.
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Diabetic cardiomyopathy (DCM) is one of the major cardiovascular complications of diabetes mellitus. Currently, there is a lack of effective treatment for DCM,and its pathophys-iology is quite complex. Mitochondria are the main source of car-diomyocyte energy and play an important role in regulating ener-gy metabolism. Mitochondria are swollen and fragmented in dia-betic patients, leading to impaired mitochondrial function, sug-gesting that mitochondrial damage and dysfunction may play an important role in the pathogenesis of DCM. In this paper, the relationship between mitochondrial damage and the pathogenesis of DCM was reviewed from the aspects of abnormal mitochondrial energy metabolism,mitochondrial oxidative stress enhancement, mitochondrial kinetics,mitochondrial heart lecithin change,and mitochondrial calcium disorder.
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This article tried to discuss that spleen deficiency is the key mechanism of hepatitis B virus associated glomerulonephritis from TCM and Western medicine viewpoint. From the view of pathophysiology, energy metabolic disorder caused by mitochondrial injury and its series of damages are similar to symptoms caused by spleen deficiency appeared as yin fire and organs dystrophy, so mitochondrial injure belongs to spleen deficiency. And mitochondrial damage can further aggravate the virus replication of hepatitis B virus associated glomerulonephritis, causing damage to the kidney. Therefore, from the view of Western medicine, it can be known that spleen deficiency determines whether the liver function damage in the process of hepatitis B virus associated glomerulonephritis and lower energizer transformation. In terms of TCM, spleen deficiency plays an important role in all stages of the disease, and determines the outcome and prognosis of the disease. Therefore, this article proposed that the spleen deficiency is the mechanism of hepatitis B virus associated glomerulonephritis, which can provide references for clinic.
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Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in renal tubular epithelial cells(RTECs)injury. Methods The male Sprague-Dawley rats were randomly divided into Sham-oper-ated and 5/6 nephrectomized group. Nephrectomized rats were further divided into two groups ,which were 4 and 8 weeks after operation,including 6 rats in each group. Rats were sacrificed at 4 or 8 weeks after nephrectomy,then control or remnant kidneys were harvested. 2μm sections of kidney tissues were collected and stained with Masson's trichrome and were graded for tubulointerstitial lesion score (TILS). RTECs mitochondrial morphology changes were detected by electron microscope. Western blot was applied to detect Cabin1 protein level in the renal tissue. Results At 8 weeks after the operation,plenty of RTECs fell off from the basement membrane,accompanied with interstitial fibrosis and the infiltration of inflammatory cells. Moreover ,TILS were significantly increased in rats at 8 weeks after operation while compared to sham-operated rats(7.16 ± 0.52 vs. 0.00 ± 0.00,P<0.05). RTECs mi-tochondria begun to swell at 4 weeks after 5/6 nephrectomy,while the disruption of cristae could be found in rats at 8 weeks. Cabin1 protein expression apparently increased in the remnant kidney. Cabin1 protein obviously increased in rats at 8 weeks after the surgery compared to sham-operated rats(0.97 ± 0.09 vs. 0.22 ± 0.07,P<0.05)and rats at 4 weeks after nephrectomy(0.97 ± 0.09 vs. 0.45 ± 0.03,P<0.05). Conclusions Cabin1 is overexpressed during RTECs injury in 5/6 nephrectomized rats. It can be a crucial factor regulating the damage of RTECs.
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Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in renal tubular epithelial cells(RTECs)injury. Methods The male Sprague-Dawley rats were randomly divided into Sham-oper-ated and 5/6 nephrectomized group. Nephrectomized rats were further divided into two groups ,which were 4 and 8 weeks after operation,including 6 rats in each group. Rats were sacrificed at 4 or 8 weeks after nephrectomy,then control or remnant kidneys were harvested. 2μm sections of kidney tissues were collected and stained with Masson's trichrome and were graded for tubulointerstitial lesion score (TILS). RTECs mitochondrial morphology changes were detected by electron microscope. Western blot was applied to detect Cabin1 protein level in the renal tissue. Results At 8 weeks after the operation,plenty of RTECs fell off from the basement membrane,accompanied with interstitial fibrosis and the infiltration of inflammatory cells. Moreover ,TILS were significantly increased in rats at 8 weeks after operation while compared to sham-operated rats(7.16 ± 0.52 vs. 0.00 ± 0.00,P<0.05). RTECs mi-tochondria begun to swell at 4 weeks after 5/6 nephrectomy,while the disruption of cristae could be found in rats at 8 weeks. Cabin1 protein expression apparently increased in the remnant kidney. Cabin1 protein obviously increased in rats at 8 weeks after the surgery compared to sham-operated rats(0.97 ± 0.09 vs. 0.22 ± 0.07,P<0.05)and rats at 4 weeks after nephrectomy(0.97 ± 0.09 vs. 0.45 ± 0.03,P<0.05). Conclusions Cabin1 is overexpressed during RTECs injury in 5/6 nephrectomized rats. It can be a crucial factor regulating the damage of RTECs.
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Sepsis is defined as life-threatening organ dysfunction caused by a dys-regulated host response to infection and septic myocardial depression (SMD) is a common complication. Pathogenesis of SMD is complicated and there is lack of specific treatment. Mitochondrial damage is an important pathological basis of SMD, and mitochondrial permeability transition pore (MPTP) plays an important role in maintaining the normal structure and function of the mitochondria. The change of MPTP during sepsis is summarized in this review so as to reveal the significant mechanism of MPTP in the occurrence of SMD.
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[ ABSTRACT] AIM:To observe the effect of high glucose on the protein expression of calreticulin ( CRT) and its association with cell apoptosis and mitochondrial dysfunction in the cardiomyocytes.METHODS: AC-16 cardiomyocytes were randomly divided into normal glucose group, high glucose group, high glucose+CRT siRNA group and isotonic con-trol group.The cell apoptotic rate, reactive oxygen species (ROS), mitochondrial membrane potential level, respiratory enzyme activity, and protein expression of CRT were observed.RESULTS: Compared with the cardiomyocytes in normal glucose group, the apoptotic rate and ROS production of cardiomyocytes increased in high glucose group, accompanying with the decreases in the mitochondrial membrane potential level and enzyme activitiy of the respiratory chain.The protein expression of CRT was significantly increased in high glucose group.However, compared with high glucose group, high glucose+CRT siRNA decreased the expression of CRT and attenuated the damage of mitochondria, but CRT siRNA did not reduce the ROS level in cardiomyocytes.CONCLUSION:High glucose brings about CRT over-expression to induce mito-chondrial injury, thus increasing myocardial apoptosis.
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This study was aimed to observe the protection ofZi-Bu Pi-Yin recipe (ZBPYR) on the cortex mitochondrial dysfunction of diabetes-associated cognitive dysfunction rats. SD rats were randomly divided into four groups, which were the control (Con) group, the diabetes (DM) group, the ZBPYR treatment (ZBPYR1) group and the ZBPYR protection (ZBPYR2) group. Morris water maze test was taken to evaluate the learning and memory ability of rats. The transmission electron microscope (TEM) was used to detect the ultrastructure and quantity changes of cortex mitochondria. Western blot was used to detect the expression of Cyto C. The results showed that compared to Con group, the learning and memory ability were decreased in the DM group (P < 0.05); the learning and memory ability of the ZBPYR1 group was improved compared to the DM group (P < 0.05); compared to the DM group, the ZBPYR2 group was significantly improved (P < 0.01). Compared with the Con group, the number of cortex mitochondria in DM group was decreased (P< 0.05), and the structure was disordered, blurred, or even completely destroyed. After ZBPYR intervention, these pathological changes were reduced obviously. And the number of mitochondria in the ZBPYR2 group was increased than that of the DM group (P < 0.05). The expression of Cyto C in cytoplasm of the DM group was significantly higher than that of the Con group (P < 0.01). After ZBPYR intervention, the expression of Cyto C was decreased. It was concluded that ZBPYR regulated the mitochondrial morphology and changes of volume in the cortex, prevented the releasing of Cyto C from mitochondria to cytoplasm, and improved the cognitive function of diabetes rats.
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Objective To observe whether calreticulin-induced mitochondrial dysfunction is involved in cardiomyocyte hypertrophy induced by angiotensin Ⅱ (AngⅡ).Methods Primary culture of neonatal rat cardiomyocytes was further confirmed by immunocytochemistry.The cardiomyocytes were randomly divided into model group,valsartan group and control group.The model group was subdivided into three groups which were separately treated with 1 0-8 mmol/L, 1 0-7 mmol/L, and 1 0-6 mmol/L Ang Ⅱ. Calreticulin expression, mitochondrial membrane potential level, enzyme activities, cell surface area and protein synthesis rate were observed.Results Cell surface area and protein synthesis rate were both increased in model groups compared with control group.Mitochondrial membrane potential level and enzyme activities were lower in model groups than in control group,while calreticulin expression was up-regulated.Pretreatment with valsartan partially reversed all the above changes.Conclusion Mitochondrial dysfunction induced by calreticulin may be an important mechanism of myocardial hypertrophy.