title: Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes.
abstract: High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes. Berberine significantly increased the AMPK activation and mitigated high glucose and/or the AMPK inhibitor, compound C-mediated mTOR activation and apoptosis in podocytes. Berberine significantly enhanced the AMPK activation and protected from high glucose-induced apoptosis in the AMPK-silencing podocytes. Furthermore, berberine significantly increased the high glucose-elevated Unc-51-like autophagy-activating kinase 1 (ULK1) S317/S555 phosphorylation, Beclin-1 expression, the ratios of LC3II to LC3I expression and the numbers of autophagosomes, but reduced ULK1 S757 phosphorylation in podocytes. In addition, berberine significantly attenuated compound C-mediated inhibition of autophagy in podocytes. The protective effect of berberine on high glucose-induced podocyte apoptosis was significantly mitigated by pre-treatment with 3-methyladenine or bafilomycin A1. Collectively, berberine enhanced autophagy and protected from high glucose-induced injury in podocytes by promoting the AMPK activation. Our findings may provide new insights into the molecular mechanisms underlying the anti-diabetic nephropathy effect of berberine and may aid in design of new therapies for intervention of diabetic nephropathy.
authors.affiliation: Department of Pharmacology, College of Basic Medical Science, Jilin University, Xinmin Street 126, Changchun 130021, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, College of Basic Medical Science, Jilin University, Xinmin Street 126, Changchun 130021, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, the First Bethune Hospital of Jilin University, Jilin University, Xinmin Street 71, Changchun 130021, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Academy of Translational Medicine, the First Bethune Hospital of Jilin University, Jilin University, Xinmin Street 71, Changchun 130021, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, College of Basic Medical Science, Jilin University, Xinmin Street 126, Changchun 130021, China. Electronic address: chan_lab@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D001599:Berberine; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; Autophagy; Berberine; High glucose; Podocyte