title: 12(S)-hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium.
abstract: 12(S)-hydroxyeicosatetraenoic acid (12-HETE) is one of the metabolites of arachidonic acid involved in pathological conditions associated with mitochondria and oxidative stress. The present study tested effects of 12-HETE on mitochondrial functions. In isolated rat heart mitochondria, 12-HETE increases intramitochondrial ionized calcium concentration that stimulates mitochondrial nitric oxide (NO) synthase (mtNOS) activity. mtNOS-derived NO causes mitochondrial dysfunctions by decreasing mitochondrial respiration and transmembrane potential. mtNOS-derived NO also produces peroxynitrite that induces release of cytochrome c and stimulates aggregation of mitochondria. Similarly, in HL-1 cardiac myocytes, 12-HETE increases intramitochondrial calcium and mitochondrial NO, and induces apoptosis. The present study suggests a novel mechanism for 12-HETE toxicity.
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Institute of Mitochondrial Biology, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Rafal R
authors.initials: RR
authors.lastname: Nazarewicz
authors.forename: Woineshet J
authors.initials: WJ
authors.lastname: Zenebe
authors.forename: Arti
authors.initials: A
authors.lastname: Parihar
authors.forename: Mordhwaj S
authors.initials: MS
authors.lastname: Parihar
authors.forename: Michael
authors.initials: M
authors.lastname: Vaccaro
authors.forename: Cameron
authors.initials: C
authors.lastname: Rink
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
authors.forename: Pedram
authors.initials: P
authors.lastname: Ghafourifar
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000008:administration & dosage*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002118:Calcium