ANG II promotes autophagy in podocytes.
Podocytes are an integral and important constituent of the glomerular filtration barrier (GFB) and are exposed to a higher concentrations of ANG II in diseased states; consequently, podocytes may accumulate oxidized proteins and damaged mitochondria. In the present study, we evaluated the effect of ANG II on the podocyte autophagic process, which is likely to be triggered in order to degrade unwanted proteins and damaged organelles. To quantitate the occurrence of autophagy, electron microscopic studies were carried out on control and ANG II-treated conditionally immortalized mouse podocytes (CIMPs). ANG II-treated cells showed a fivefold greater number of autophagosomes/field compared with control cells. This proautophagic effect of ANG II was inhibited by pretreatment with 3-methyladenine, an inhibitor of autophagy. ANG II also enhanced podocyte expression of autophagic genes such as LC3-2 and beclin-1. Since oxidative stress is often associated with the induction of autophagy, we examined the effect of ANG II on podocyte reactive oxygen species (ROS) generation. ANG II enhanced podocyte ROS generation in a time-dependent manner. To determine whether there is a causal relationship between ANG II-induced oxidative stress and induction of autophagy, we evaluated the effect of antioxidants on ANG II-induced autophagy. As expected, the proautophagic effect of ANG II was inhibited by antioxidants. We conclude that ANG II promotes podocyte autophagy through the generation of ROS.
Yadav
Anju
A
Department of Medicine, North Shore and Long Island Jewish Health System and Feinstein Institute for Medical Research, Manhasset, New York, USA.
Vallabu
Sridevi
S
Arora
Shitij
S
Tandon
Pranay
P
Slahan
Divya
D
Teichberg
Saul
S
Singhal
Pravin C
PC
D000804:Angiotensin II / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D050199:Podocytes / Q000502:physiology* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D000804:Angiotensin II