title: Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro.
abstract: Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Xu-Shun
authors.initials: XS
authors.lastname: Jiang
authors.affiliation: Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Jiang-Min
authors.initials: JM
authors.lastname: Wan
authors.affiliation: Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Gui
authors.affiliation: Centre for Nephrology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, United Kingdom.|Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Xiong-Zhong
authors.initials: XZ
authors.lastname: Ruan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.|Laboratory of Lipid &Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D019308:Palmitic Acid / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D002738:Chloroquine