12(S)-hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium.

Nazarewicz RR, Zenebe WJ, Parihar A, Parihar MS, Vaccaro M, Rink C, Sen CK, Ghafourifar P
Arch Biochem Biophys. 2007 468 (1): 114-20

PMID: 17963719 · PMCID: PMC2210014 · DOI:10.1016/j.abb.2007.09.018

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.

MeSH Terms (10)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid Animals Calcium Cells, Cultured Dose-Response Relationship, Drug Mitochondria, Heart Myocytes, Cardiac Nitric Oxide Rats Rats, Sprague-Dawley

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