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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cellular physiology and biochemistry 2015-01, Vol.35 (3), p.1201-1218
Hauptverfasser: Nie, Huibin, Xue, Xia, Li, Jie, Liu, Xiangchun, Lv, Shasha, Guan, Guangju, Liu, Haiying, Liu, Gang, Liu, Shanshan, Chen, Zhixin
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
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.
ISSN:1015-8987
1421-9778
DOI:10.1159/000373944