Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes

Kidney and Blood Pressure Research

Gao X.²  Cai J.²  Wang W.²  Mou Z.¹  Wu Y.¹  Tang S.²  Zhang Y.²  Zhang J.²  Wang L.¹  Xie L.² 

[1] Department of Nephrology, Xinqiao Hospital, $$

关键词: NADPH oxidase;    p47-phox;    Podocyte;    Angiotensin II;    Autophagy;    Sinomenine;   

DOI  :  10.1159/000443417

来源: S Karger AG

【 摘 要 】

Background/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. Methods: Podocytes were pretreated with graded concentrations (10^-8 M ∼ 10^-4 M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. Results: The 10^-8 M ∼ 10^-4 M of SN alone did not effect ROS generation or podocyte autophagy. The 10^-8 M and 10^-6 M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. Conclusion: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane.

【 授权许可】

Unknown