title: Nitro-oleic acid attenuates OGD/R-triggered apoptosis in renal tubular cells via inhibition of Bax mitochondrial translocation in a PPAR-γ-dependent manner.
abstract: BACKGROUND
  Nitroalkene derivatives of oleic acid (OA-NO2) serve as high-affinity ligand for PPAR-γ, which regulates apoptosis, oxidation and inflammation and plays a central role in ischemia-reperfusion injury. In the present study, we elucidated the protective mechanisms of OA-NO2 against renal ischemia-reperfusion injury.
  
  
  METHODS
  HK-2 cells were subjected to oxygen and glucose deprivation followed by re-oxygenation (OGD/R) to mimic renal ischemia-reperfusion injury. Cell apoptosis was analyzed by flow cytometry. Bax mitochondrial translocation, cytochrome c and apoptosis-inducing factor (AIF) cytosolic leakage and Akt/Gsk 3β phosphorylation were evaluated by Western blotting. Bax activation was visualized by immunocytochemistry. GW9662 and siRNA transfection were employed to examine the involvement of PPAR-γ.
  
  
  RESULTS
  OGD/R injury promoted mitochondrial translocation and activation of Bax, leakage of cytochrome c and AIF, subsequent caspase-3 activation, and eventually cell apoptosis. Pre-incubation with OA-NO2 (1.25 µM, 45min) inhibited Bax activation and blocked apoptotic cascade, while the protective effects were negated by GW9662 or PPAR-γ siRNA. Moreover, OA-NO2 restored Akt and Gsk 3β phosphorylation in a PPAR-γ-dependent way.
  
  
  CONCLUSIONS
  These findings suggest that OA-NO2 attenuates OGD/R-induced apoptosis by inhibiting Bax translocation and activation and the subsequent mitochondria-dependent apoptotic cascade in a PPAR-γ dependent manner.
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Nie
authors.forename: Xia
authors.initials: X
authors.lastname: Xue
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Liu
authors.forename: Shasha
authors.initials: S
authors.lastname: Lv
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000813:Anilides / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D045304:Cytochromes c / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D019301:Oleic Acid / Q000008:administration & dosage*; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D051033:Apoptosis Inducing Factor; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019301:Oleic Acid; D045304:Cytochromes c; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3