title: CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.
abstract: BACKGROUND
  Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN), respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.
  
  
  METHODS
  The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20) by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5) and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.
  
  
  RESULTS
  CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO), the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol) inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.
  
  
  CONCLUSIONS
  CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Medical College Road 1, Chongqing, 400016, China.
authors.forename: Hui-zhe
authors.initials: HZ
authors.lastname: Huang
authors.affiliation: Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400042, China.
authors.forename: Lan-ting
authors.initials: LT
authors.lastname: Tan
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: Faculty of Basic Medical Sciences, Chongqing Medical University, Medical College Road 1, Chongqing, 400016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
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: 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; 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 / Q000187:drug effects / Q000502:physiology*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009829:Oleic Acids / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D019308:Palmitic Acid / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D013388:Succinimides / Q000494:pharmacology
chemical_list: D018955:CD36 Antigens; D003497:Cyclic N-Oxides; D009829:Oleic Acids; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013388:Succinimides; C120556:sulfo-N-succinimidyl oleate; D019308:Palmitic Acid; C001803:tempol