Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes

• Published in: European journal of pharmacology Vol. 794; pp. 106 - 114
• Main Authors: Jin, Yingli, Liu, Shuping, Ma, Qingshan, Xiao, Dong, Chen, Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2017
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Berberine; Berberine - pharmacology; Cell Survival - drug effects; Cytoprotection - drug effects; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Glucose - pharmacology; High glucose; Mice; Phosphorylation - drug effects; Podocyte; Podocytes - cytology; Podocytes - drug effects; Podocytes - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Podocyte; Berberine; AMPK; Autophagy; High glucose
• DOI: 10.1016/j.ejphar.2016.11.037
• ISSN: 0014-2999

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.