title: Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction in a Cell Line of Kidney Proximal Tubular Cells.
abstract: Nitro-arachidonic acid (NO2-AA) is a cell signaling nitroalkene that exerts anti-inflammatory activities during macrophage activation. While angiotensin II (ANG II) produces an increase in reactive oxygen species (ROS) production and mitochondrial dysfunction in renal tubular cells, little is known regarding the potential protective effects of NO2-AA in ANG II-mediated kidney injury. As such, this study examines the impact of NO2-AA on ANG II-induced mitochondrial dysfunction in an immortalized renal proximal tubule cell line (HK-2 cells). Treatment of HK-2 cells with ANG II increases the production of superoxide (O2●-), nitric oxide (●NO), inducible nitric oxide synthase (NOS2) expression, peroxynitrite (ONOO-) and mitochondrial dysfunction. Using high-resolution respirometry, it was observed that the presence of NO2-AA prevented ANG II-mediated mitochondrial dysfunction. Attempting to address mechanism, we treated isolated rat kidney mitochondria with ONOO-, a key mediator of ANG II-induced mitochondrial damage, in the presence or absence of NO2-AA. Whereas the activity of succinate dehydrogenase (SDH) and ATP synthase (ATPase) were diminished upon exposure to ONOO-, they were restored by pre-incubating the mitochondria with NO2-AA. Moreover, NO2-AA prevents oxidation and nitration of mitochondrial proteins. Combined, these data demonstrate that ANG II-mediated oxidative damage and mitochondrial dysfunction is abrogated by NO2-AA, identifying this compound as a promising pharmacological tool to prevent ANG II-induced renal disease.
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Calvo
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cassina
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rios
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Peluffo
authors.affiliation: Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
authors.forename: José
authors.initials: J
authors.lastname: Boggia
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Homero
authors.initials: H
authors.lastname: Rubbo
authors.affiliation: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Andres
authors.initials: A
authors.lastname: Trostchansky
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D000804:Angiotensin II; D030421:Peroxynitrous Acid; D016718:Arachidonic Acid; D019001:Nitric Oxide Synthase; D013385:Succinate Dehydrogenase; D000251:Adenosine Triphosphatases