Early autophagy activation inhibits podocytes from apoptosis induced by aldosterone / 中华肾脏病杂志

ABSTRACT

Objective To explore the protection of early autophagy activation on podocyte injury induced by aldosterone.Methods In vitro cultured mouse podocyte clones (MPC5) were treated with aldosterone for 6,12,24,48 h respectively.Apoptosis of podocytes was detected by Annexin V combined with flow cytometry.After 24 h treatment with aldosterone,the existence of apoptotic body and autophagosome was observed by electron microscopy.The protein expressions of LC3,caspase-3 and nephrin were examined by Western blotting.The mRNA expression of Beclin-l was detected by real-time PCR.Results The induction of apoptosis and autophagy by aldosterone in podocytes was in timedependent mannner.After 24 h treatment with aldosterone,the apoptosis was increased by 26.5％ (P ＜ 0.05)and the expression of nephrin was decreased by 28.0％ (P ＜ 0.05) compared to control group.Aldosterone remarkably induced the expression of Beclin-1 at 6 h and promoted the transformation of LC3-Ⅰ to LC3-Ⅱat 12 h (P ＜ 0.05).Compared to simple aldosterone treatment,the apoptosis rate of podocyte was increased by 39.0％ (P ＜ 0.05) and the expression of nephrin was declined by 19.5％ (P ＜ 0.05) after 3-methyladenine (3-MA) pre-treatment.Conclusions Aldosterone can induce autophagy and apoptosis in podocytes.Autophagy occurs earlier (12 h) than apoptosis (24 h).The occurrence of autophagy can inhibit the apoptosis,so the autophagy pathway may be a new research topic of glomerular disease treatment.