Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction in a Cell Line of Kidney Proximal Tubular Cells

Autor: Andrés Trostchansky, Adriana Cassina, Natalia Rios, Gonzalo Peluffo, Beatriz Sánchez-Calvo, José Boggia, Rafael Radi, Homero Rubbo
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Physiology
Cell Membranes
lcsh:Medicine
030204 cardiovascular system & hematology
Mitochondrion
Biochemistry
chemistry.chemical_compound
0302 clinical medicine
Medicine and Health Sciences
lcsh:Science
Energy-Producing Organelles
Kidney
Multidisciplinary
biology
Superoxide
Respiration
Chemical Reactions
Neurochemistry
Mitochondria
Nitric oxide synthase
Chemistry
medicine.anatomical_structure
Physical Sciences
cardiovascular system
Cellular Structures and Organelles
Anatomy
Neurochemicals
Peroxynitrite
Research Article
inorganic chemicals
medicine.medical_specialty
Cell Physiology
Nitration
Bioenergetics
Nitric Oxide
Nitric oxide
03 medical and health sciences
Oxygen Consumption
Internal medicine
Oxidation
medicine
lcsh:R
Biology and Life Sciences
Membrane Proteins
Kidneys
Cell Biology
Renal System
Angiotensin II
Peroxynitrous acid
030104 developmental biology
Endocrinology
chemistry
biology.protein
lcsh:Q
Cell Immortalization
Physiological Processes
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 3, p e0150459 (2016)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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