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Objective:To investigate the immunoregulatory effects of Glycyrrhiza uralensis ethanol extract(GUEE) on the maturation of dendritic cells (DCs) and the adjuvant effect of GUEE on OVA in na?ve BALB/c mice and an ovalbumin (OVA)-induced asthma mouse model. Methods:GUEE was prepared, and the effects of different concentrations of GUEE on the maturation of DCs and the secreted cytokines as well as the effects of GUEE on bacterial lipopolysaccharide (LPS)-induced DC maturation were examined in vitro. The effect of GUEE on the morphology of mouse bone marrow derived DCs was observed using microscopy. Molecular expression levels on the surface of DCs were detected using flow cytometry. The levels of interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in the supernatant of DCs cultures were measured by enzyme-linked immunosorbent assay (ELISA). The maturation status of DCs was detected by flow cytometry by injecting different concentrations of GUEE into the paws of mice and isolating the draining lymph nodes 24 h later. The naive BALB/c mice were co-immunized with OVA, and the changes in regulatory T cells (Treg) were detected by flow cytometry. An OVA-protein-induced mouse asthma model was established to investigate whether GUEE as a tolerogenic adjuvant has an antigen-specific therapeutic effect on asthmatic mice. Pulmonary pathological changes were analyzed by hematoxylin-eosin staining (HE) and PAS staining. OVA-specific antibodies in serum and the frequencies of Tregs, CD4 + IFN-γ + and CD4 + IL-4 + T cells in the spleen were detected by ELISA and flow cytometry, respectively. Results:GUEE suppressed DCs maturation induced by LPS both in vitro and in vivo (all P<0.05), and reduced proinflammatory cytokine production, including IL-1β, IL-6, IL-12 and TNF-α in the absence or presence of LPS (all P<0.05). Moreover, co-immunization with OVA and GUEE increased the amount of Tregs in na?ve BALB/c mice ( P<0.05). In OVA-induced asthmatic mice, OVA and GUEE co-immunization and GUEE alone treatment substantially ameliorated the inflammation of lung tissues, decreased the levels of IgG 1 and the amount of CD4 + IL-4 + T cells, and increased the amount of Tregs (all P<0.05). Conclusions:GUEE alone or as the tolerogenic adjuvant can ameliorate allergic diseases through inhibition of DC maturation and type 2 helper T cell responses and induction of Tregs.
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Objective:To analyze data safety problem raised from personal medical data sharing and privacy protection, provide suggestions for improving its application and development.Methods:The personal medical data sharing and privacy protection measures were discussed according to the study of related literatures, typical case analysis, analyzing the current situation and its development trend of legislation status of personal medical data sharing and privacy protection.Results:Medical data is one kind of personal data, but more sensitive than other personal data. The country should strengthen relevant legislation, more clearly define relevant concepts, establish the authority and scope of personal medical data processing, improve the effectiveness and operability of laws, maximize the public interest of data, and ensure the balance between the personal data processing and privacy security.Conclusions:The personal medical data sharing and privacy protection is a systematic project. The solution of the personal security risks is also based on a comprehensive safeguard system which including laws, regulations, management and technology.
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Regulated necrosis is a newly discovered new cell death pathway, including necroptosis, pyroptosis and ferroptosis. It has been reported to play a key role in acute kidney injury (AKI) induced by ischemia/reperfusion, cisplatin and other drugs, and rhabdomyolysis. Studying the role of regulated necrosis-related pathways in AKI is expected to provide a new direction for clarifying the pathogenesis and treatment of AKI, with potential therapy and application prospects. In this review, we summarize the related signaling pathways of necroptosis, pyroptosis and ferroptosis, and the related research progress in AKI, in order to provide potential targets for the prevention and treatment of AKI.
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Objective:To understand the management status of breast cancer-related lymphedema, and to provide a basis for the formulation of prevention and treatment plans for breast cancer-related lymphedema.Methods:Using accidental sampling, a questionnaire designed by the research team was used to survey nurses in 58 hospitals in Jiangsu Province.Results:This study surveyed a total of 58 hospitals, of which 53 were general hospitals and 5 specialized hospitals. Only 11 hospitals (18.97%) had treatment rooms dedicated to conservative treatment of lymphedema, 9 hospitals (15.52%) had opened lymphedema clinics, and 15 hospitals (25.86%) had professional international lymphedema therapists. All the 58 hospitals had different degrees of prevention and management of breast cancer-related lymphedema.Conclusions:The comprehensive management of lymphedema has not yet been achieved, and the management standards of lymphedema also need to be further improved. It is important to establish a unified and standardized management plan and practice standards.
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Objective:To investigate the correlations of dynamic iodine nutrition status and thyroid function in pregnant women and newborns in Lingang of Shanghai, so as to provide an evidence for whether urine iodine testing and iodine supplementation should be carried out.Methods:A prospective study was conducted by randomly selecting pregnant women from October 2017 to October 2018 in Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health Sciences. The pregnant women were divided into early (5-12 weeks), middle (22-24 weeks), late pregnancy (36-37 weeks). Samples of serum and 24 hours urine were collected to test on thyrotropin (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroid peroxidase (TPOAb), anti-thyroglobulin (TgAb) and urinary iodine. TSH in neonatal heel blood was analyzed 72 h after birth (newborns from pregnant women in the late pregnancy). The differences of thyroid function of pregnant women with different pregnant periods and different urinary iodine levels were analyzed, as well as the neonatal TSH levels of pregnant women with different urinary iodine levels. Results:A total of 109, 90 and 54 cases of pregnant women in early, middle and late pregnancy were investigated and the medians of urinary iodine were 120.95, 136.30 and 116.80 μg/L, respectively. There was no significant difference in urinary iodine content among different pregnant periods( P > 0.05). The proportions of urinary iodine level less than 150 μg/L in early, middle and late pregnancy were 75.2% (82/109), 61.1% (55/90) and 59.3% (32/54), respectively. The median values of serum TSH in early, middle and late pregnancy were 1.81, 1.95 and 2.29 mU/L, mean values of FT 3 were (5.21 ± 0.84), (4.79 ± 0.72) and (4.13 ± 0.56)pmol/L, and means of FT 4 were (16.48 ± 2.58), (15.02 ± 2.78) and (13.31 ± 1.87) pmol/L, respectively. The FT 3 and FT 4 levels in the late pregnancy were lower than those in the early and middle pregnancy, while the TSH levels in the late pregnancy were higher than those in the early and middle pregnancy. There were no significant difference in serum FT 3, FT 4 and TSH levels among early, middle and late pregnancy under different urinary iodine levels. The median TSH of newborn heel blood was 1.48 mU/L. There was no statistically significant difference between the neonatal heel blood TSH level of pregnant women with urinary iodine < 150 μg/L [1.45(1.09, 2.23)mU/L] in late pregnancy and those with urinary iodine ≥150 μg/L [1.42 (1.14, 2.61) mU/L, Z=- 0.354, P > 0.05]. Conclusions:There is mild iodine deficiency in pregnant women in Lingang of Shanghai. However, due to the compensatory regulation, it has no significant effect on the thyroid function of mother and newborn. Monitoring of iodine nutrition of pregnant women should be carried out and iodine supplementation should be done scientifically and reasonably.
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Objective:The work aims to analyze the effect of berberine on the transcriptome-feature of the methicillin-resistant Staphylococcus aureus (MRSA) USA300 by using transcriptome sequencing (RNA-seq methods) methods and to investigate the bacteriostatic mechanism of berberine on MRSA. Methods:Basic research. The standard strain USA300 was used in this study, which was a honorable gift from Dr. Lan Lefu in Shanghai Institute of medicine, Chinese Academy of Sciences in 2019. The differential gene expression profiles of berberine treated [1/2 MIC (64 mg/L) and 1/8 MIC (16 mg/L), respectively] and untreated USA300 were analyzed. The screening conditions for differentially expressed genes were set as: P-Value<0.05, and the | Fold-change |>2. SPSS 20.0 was used to analyze the result. Results:Sequencing results showed that there were 754 differentially expressed genes in the high concentration group compared with the normal control group, of which the up-regulated genes were lukD, lukE, ssaA, etc., while the down-regulated genes were lukF-PV, lukS-PV, clfA, splB-splF, sspA,etc.. Only 19 genes were differentially expressed in the low concentration group compared with the normal control group, of which the up-regulated genes were speG, scpB, rpsQ,etc., while the down-regulated genes were beta,bccT, etc.Conclusions:In this study, the gene expression of USA300 transcriptome was studied to understand the differential gene expression after berberine treatment. It was speculated that berberine played a role in inhibiting MRSA by regulating the hydrolysis of bacterial cell wall, the expression of leucotoxin and other virulence factors.
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Objectives:To investigate the risk factors of sarcopenia in patients receiving maintenance peritoneal dialysis (MPD).Methods:One hundred and thirteen patients receiving maintenance MPD for ≥3 months during January and December 2017 were enrolled in this study. According to the Asian Working Group for Sarcopenia(AWGS)algorithm, there were 26 patients with sarcopenia accounting for 23.0% of all MPD patients. Demographic and anthropometric data were collected; laboratory tests were conducted, Kt/V urea and normalized protein equivalent of total nitrogen appearance were calculated; the bioelectrical impedance analysis (BIA) was performed and grip strength was tested. The nutritional status was evaluated with Subjective Global Assessment (SGA). Logistic regression was used to analyze the risk factors of sarcopenia in MPD patients. Results:BMI and dialysis dose of patients with sarcopenia were significantly lower than those without sarcopenia [(20.35±2.35) kg/m 2vs. (23.81±3.14) kg/m 2, t=-5.181, P<0.01; (5.57±1.83) L/d vs. (6.66±1.71) L/d, t=-2.795, P<0.01]. The bioelectrical impedance analysis showed that the total water content of patients with sarcopenia was higher than that of patients without sarcopenia [(35.44±6.40) kg vs. (28.52±4.89) kg, t=5.077, P<0.01]; while the protein content[(7.46±1.31) kg vs. (9.24±1.63) kg, t=-5.080, P<0.01] and skeletal muscle content [(20.54±4.18) kg vs. (25.88±4.95) kg, t=-4.980, P<0.01] of patients with sarcopenia were lower than those without sarcopenia. Multivariate analysis showed that decreased BMI( OR=0.934, 95 %CI: 0.723-0.998, P<0.01) and body protein ( OR=0.927, 95 %CI: 0.698-0.996, P<0.01), increased total body water( OR=1.382, 95 %CI: 1.053-1.813, P=0.02) were independent risk factors for sarcopenia in MPD patients. Conclusion:The incidence of sarcopenia in MPD patients is high, which is associated with the excessive volume load and malnutrition of patients.
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Objective@#To investigate the relationships between behavioral problems and family environment in obese children aged 6-15 years to provide a dereference for the analysis of behavioral problems among obese children and the construction of their family environmet .@*Methods@#Family environment dimensions and behavioral problems were investigated among 2 376 obese children and 2 376 non-obese children with Family Environment Scale Symptoms Questionnaire and Achenbach Child Behavior Checklist. Data were analyzed by SPSS 17.0.@*Results@#The incidence of the behavioral problems in obese children (21.12%) was higher than that of non-obese children (15.53%)(χ2=24.93，P<0.01).The scores of Family Environment Scale Symptoms Questionnaire differed between obese children and nonobese children (Z=-2.44, -2.98, -3.38, P<0.05). Binary logistic regression results showed that for obese boys and girls aged 6 to 11 years, high maternal education levels(OR=0.78, 95%CI=0.69-0.88), family cohesion(OR=0.75, 95%CI=0.67-0.84) and less family conflicts(OR=0.81, 95%CI=0.75-0.87) were related to less behavioral problems; for obese boys and girls aged 12 to 15 years, family cohesion(OR=0.79, 95%CI=0.70-0.90) and less family conflicts(OR=0.78, 95%CI=0.71-0.86) were related to less behavioral problems.@*Conclusion@#Family cohesion and less family conflicts might help low the risk of behavioral problems among obese children. The role of family environment on behavioral problems should not be neglected in future mental health promotion and social work service for obese children.
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Objective To investigate the effects of water extracts of Lepidium meyenii walp (LMWE) collected from two different places in Xinjiang on the maturation and function of dendritic cells (DCs) and to evaluate their roles in immunoregulation. Methods Water extracts of LMWE growing in Tashikuergan County (Ta xian) and A La gou of Xinjiang were prepared and named as LMWE-T and LMWE-A,respectively. Bone marrow-derived DCs and splenocytes isolated from C57BL/6 mice were treated with different concentrations of polysaccharide extracts from LMWE-T/A. Effects of LMWE-T/A on the per-centage and apoptosis of DC,expression of co-stimulatory molecules and secretion of cytokines were detected by flow cytometry and ELISA. MTT assay was used to analyze the proliferation of splenocytes. Changes in the functions of DC were evaluated by mixed lymphocyte reaction(MLR). Results LMWE-T/A had no in-fluence on the percentage and viability of DC. Expression of CD40 and CD86,and secretion of TNF-α,IL-12p40 and IFN-γ were significantly increased by LMWE-T/A treatment in a dose-dependent manner. LMWE-T/A treatment enhanced the functions of DCs and also dose-dependently promoted the proliferation of splenocytes. LMWE-A was more effective than LMWE-T in promoting CD86 expression,IFN-γ secretion and splenocyte proliferation. Pretreatment with TAK-242,an inhibitor of Toll-like receptor 4(TLR4),could sig-nificantly inhibit the regulatory effects of LMWE-T/A on CD40 expression and the secretion of TNF-α and IL-12p40. Conclusion This study shows that LMWE could promote the maturation of DC through TLR4 signaling pathway,enhance the functions of DC without side effects on DC survival,and increase the prolif-eration of splenocytes,indicating that LMWE has a potential immunopotentiating effect. LMWE-A has better effects than LMWE-T on immune enhancement.
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Objective To explore the effects of C/EBPα knockout in podocyte on diabetic nephropathy and its mechanisms.Methods C/EBPαloxp/loxp mice were crossed with podocin-cre mice to obtain F1 hybrids and then propagated until homozygous mice (C/EBPαf/f) were obtained.Diabetic nephropathy (DN) models were established by low-dose streptozotocin (STZ,100 mg/kg) administration after 25 weeks of normal diet or 45％ high-fat diet treatment,and biochemical indicators of blood and urea were measured.The morphological characteristics and the proteins regulating oxidative stress and mitochondrial function were detected.Results The type 2 DN models were successfully constructed based on transgenic mice.The kidneys of 8-month-old C/EBPαf/f mice did not show obvious morphological changes,but after constructing DN models,they showed obvious renal impairment,inflammation and oxidative stress.Compared with wild-type DN mice,the protein levels of nephrin and E-cadherin in DN C/EBPαf/f mice with DN were significantly decreased (P ＜ 0.01);fibronectin and Nrf2 protein levels were all increased (all P ＜ 0.05).Keap1,phospho-AMPK and mitochondrial function related genes Pgc-1α protein levels were all decreased (all P ＜ 0.05).Conclusion Podocyte C/EBPα knockout exacerbates diabetic nephropathy by promoting fibrosis and inhibiting Pgc-1α-mediated mitochondrial antioxidant function.
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Acute kidney injury (AKI) is a frequent syndrome in hospitalized patients .Recently, a number of studies have been reported that the close relationship exists between genetic polymorphism and AKI .The current research on genetic polymorphism related with AKI is reviewed in this article .
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Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
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Humans , Apoptosis , Cell Line, Tumor , Enzyme Activation , Ligands , Molecular Docking Simulation , Nuclear Receptor Subfamily 4, Group A, Member 1 , Genetics , Metabolism , Oximes , Metabolism , Pharmacology , Protein Conformation , Proto-Oncogene Proteins c-akt , Metabolism , Pyrazoles , Metabolism , Pharmacology , Retinoid X Receptor alpha , Chemistry , Genetics , Metabolism , Thiazoles , Metabolism , Pharmacology , Transcription, Genetic , Transcriptional Activation , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
[ ABSTRACT] AIM:To investigate the effect of paricalcitol ( P) on renal tubulointerstitial fibrosis and the under-lying mechanisms in diabetic nephropathy ( DN) .METHODS:DN rat model was induced by a single intraperitoneal in-jection of streptozotocin after fasting.The animals were randomly divided into 2 groups: the DN rats in paricalcitol-inter-vened group ( group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4μg/kg (3 times a week);the DN rats in DN group ( group D) were given isopyknic propylene glycol.Normal control group ( group C) was also set up.The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks.The biochemical indexes were measured.The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4,β-catenin and Klotho by immunohistochemistry and Western blotting.In addition, the correlation among the above indexes was analyzed.RESULTS:(1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D ( P<0.05 ) .( 2 ) The area of renal tubulointerstitial fibrosis in-creased in group D compared with group C, while decreased in group P compared with group D (P<0.05).(3) The ex-pression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05).Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 andβ-catenin decreased in group P (P<0.05).(4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 andβ-catenin (P<0.05).CONCLUSION:Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.
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Transforming growth factor-β (TGF-β) members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II (TβR II) and type I (TβRI) and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes (DUBs). In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regulatory roles of these DUBs as a driving force for cancer progression as well as their underlying working mechanisms are also discussed.
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Animals , Humans , Molecular Targeted Therapy , Receptors, Transforming Growth Factor beta , Metabolism , Signal Transduction , Smad Proteins , Physiology , Transforming Growth Factor beta , Physiology , Ubiquitin Thiolesterase , Metabolism , Ubiquitin-Specific Proteases , UbiquitinationABSTRACT
The Wnt/β-catenin and bone morphogenetic proteins (BMPs) pathways play important roles in controlling osteogenesis. Using a cell-based kinase inhibitor screening assay, we identified the compound bisindoylmaleimide I (BIM) as a potent agonist of the cytosolic β-catenin accumulation in preosteoblast cells. Through suppressing glycogen synthase kinase 3β enzyme activities, BIM upregulated β-catenin responsive transcription and extended duration of BMP initiated signal. Functional analysis revealed that BIM promoted osteoblast differentiation and bone formation. The treatment of human mesenchymal stem cells with BIM promoted osteoblastogenesis. Our findings provide a new strategy to regulate mesenchymal stem cell differentiation by integration of the cellular signaling pathways.
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Animals , Mice , Bone Morphogenetic Proteins , Metabolism , Cell Differentiation , Cell Line, Tumor , Glycogen Synthase Kinase 3 , Metabolism , Glycogen Synthase Kinase 3 beta , Indoles , Chemistry , Pharmacology , Maleimides , Chemistry , Pharmacology , Mesenchymal Stem Cells , Cell Biology , Metabolism , Osteoblasts , Cell Biology , Metabolism , RNA Interference , RNA, Small Interfering , Metabolism , Signal Transduction , Wnt Proteins , Metabolism , beta Catenin , Genetics , MetabolismABSTRACT
We investigate the role of β-catenin signaling in the response of macrophage to lipopolysaccharide (LPS) using RAW264.7 cells. LPS rapidly stimulated cytosolic β-catenin accumulation. β-catenin-mediated transcription was showed to be required for LPS induced gene expression and cell migration. Mechanically, ERK activation-primed GSK3β inactivation by Akt was demonstrated to mediate the LPS induced β-catenin accumulation. Overall, our findings suggest that suppression of GSK3β by ERK stimulates β-catenin signaling therefore contributes to LPS induced cell migration in macrophage activation.
Subject(s)
Animals , Mice , Cell Line , Cell Movement , Enzyme Activation , Extracellular Signal-Regulated MAP Kinases , Metabolism , Gene Expression Regulation, Enzymologic , Glycogen Synthase Kinase 3 , Metabolism , Glycogen Synthase Kinase 3 beta , Lipopolysaccharides , Pharmacology , Macrophages , Cell Biology , Metabolism , Matrix Metalloproteinase 9 , Genetics , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction , Transcription, Genetic , Wnt Proteins , Metabolism , beta Catenin , MetabolismABSTRACT
ObjectiveTo study the effect of 1,25-(OH)2D3 analogs paricalcitol on proteinuriaindiabeticnephropathy (DN)rats, andtoinvestigateitspossiblemechanism.Methods DN model rats were established by intraperitoneal injection with streptozotocin.All the DN rats were randomly divided into the paricalcitol group(group P ) and DN group(group D).Healthy rats were chosen as healthy control group(group N).24-h urinary protein and serum biochemical indicators were examined after 12 weeks.ELISA was applied to detect the level of renin and Ang Ⅱ in the kidney.Immunohistochemistry and real-time PCR were used to detect the protein and mRNA expression of heparanases(HPA)and podoein.Results Compared with group N,24-h urinary protein,serum creatinine,renin and Ang Ⅱ in group D and group P were markedly increased,and they were significantly higher in group D as compared to group P (all P＜0.05).Compared with group N,the expression of HPA protein and mRNA in group D and group P increased markedly,and higher expression was found in group D(all P＜0.05).The expression of podocin protein and mRNA in group D and group P decreased markedly,and lower expression was found in group D(all P＜0.05).Renin level was positively correlated with HPA protein expression (r=0.78,P＜O.OS),negatively correlated with podocin protein expression(r=-0.63,P＜O.05),and not correlated with their mRNA expression.Conclusion Paricalcitol can significantly reduce the proteinuria,which may be associated with the inhibition of renin by down-regulating protein expression of HPAin glomerular basement membrane and up-regulating protein expression of podocin in podocyte.
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Amyloid beta (Aβ) precursor protein (APP) is a key protein in the pathogenesis of Alzheimer's disease (AD). Both APP and its paralogue APLP1 (amyloid beta precursor-like protein 1) have multiple functions in cell adhesion and proliferation. Previously it was thought that autophagy is a novel beta-amyloid peptide (Aβ)-generating pathway activated in AD. However, the protein proteolysis of APLP1 is still largely unknown. The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses, such as proteasome inhibition. Activation of the endoplasmic reticulum (ER) stress by proteasome inhibitors induces autophagy, causing reduction of mature APLP1/APP. Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1. Therefore, our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.