title: Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.
abstract: Nitroalkene derivative of oleic acid (OA-NO2), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO2attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO2in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO2(1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO2promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO2inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22phoxup-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO2reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.|b Department of Nephrology , Chengdu First People's Hospital , Chengdu , Sichuan , PR China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Nie
authors.affiliation: c Department of Pharmacy , The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xue
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University , Jinan , Shandong , PR China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D019255:NADPH Oxidases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019301:Oleic Acid; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D019255:NADPH Oxidases; D005947:Glucose; D010100:Oxygen
keywords: NADPH oxidase; Nrf2; Oxygen and glucose deprivation/re-oxygenation; nitro-oleic acid; oxidative stress