Nitro-Oleic Acid Attenuates OGD/R-Triggered Apoptosis in Renal Tubular Cells via Inhibition of Bax Mitochondrial Translocation in a PPAR-γ-Dependent Manner
Background: Nitroalkene derivatives of oleic acid (OA-NO 2 ) 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-NO 2 against renal...
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Veröffentlicht in: | Cellular physiology and biochemistry 2015-01, Vol.35 (3), p.1201-1218 |
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Sprache: | eng |
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Zusammenfassung: | Background: Nitroalkene derivatives of oleic acid (OA-NO 2 ) 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-NO 2 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-NO 2 (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-NO 2 restored Akt and Gsk 3β phosphorylation in a PPAR-γ-dependent way. Conclusion: These findings suggest that OA-NO 2 attenuates OGD/R-induced apoptosis by inhibiting Bax translocation and activation and the subsequent mitochondria-dependent apoptotic cascade in a PPAR-γ dependent manner. |
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ISSN: | 1015-8987 1421-9778 |
DOI: | 10.1159/000373944 |