title: Heart mitochondrial nitric oxide synthase. Effects of hypoxia and aging.
abstract: The production of NO by heart mitochondria was 0.7-1.1 nmol NO/min.mg protein, an activity similar to the ones observed in mitochondrial membranes from other organs. Heart mtNOS seems to contribute with about 56% of the total cellular NO production. The immunological nature of the mtNOS isoform of cardiac tissue remains unclear; in our laboratory, heart mtNOS reacted with an anti-iNOS anti-body. Heart mtNOS expression and activity are regulated by physiological and pharmacological effectors. The state 4/state 3 transition regulates heart mtNOS activity and NO release in intact respiring mitochondria: NO production rates in state 3 were 40% lower than in state 4. Heart mtNOS expression was selectively regulated by O(2) availability in hypobaric conditions and the activity was 20-60% higher in hypoxic rats than in control animals, depending on age. In contrast, NADH-cytochrome c reductase and cytochrome oxidase activities were not affected by hypoxia. The activity of rat heart mtNOS decreased 20% on aging from 12 to 72 weeks of age. On the pharmacological side, mitochondrial NO production was increased after enalapril treatment (the inhibitor of the angiotensin converting enzyme) with modification of heart mtNOS functional activity in the regulation of mitochondrial O(2) uptake and H(2)O(2) production. Thus, heart mtNOS is a highly regulated mitochondrial enzyme, which in turn, plays a regulatory role through mitochondrial NO steady state levels that modulate O(2) uptake and O(2)(-) and H(2)O(2) production rates. Nitric oxide and H(2)O(2) constitute signals for metabolic control that are involved in the regulation of cellular processes, such as proliferation and apoptosis.
authors.affiliation: Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. lbvaldez@ffyb.uba.ar
authors.forename: Laura B
authors.initials: LB
authors.lastname: Valdez
authors.forename: Tamara
authors.initials: T
authors.lastname: Zaobornyj
authors.forename: Silvia
authors.initials: S
authors.lastname: Alvarez
authors.forename: Juanita
authors.initials: J
authors.lastname: Bustamante
authors.forename: Lidia E
authors.initials: LE
authors.lastname: Costa
authors.forename: Alberto
authors.initials: A
authors.lastname: Boveris
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000502:physiology*
chemical_list: D019001:Nitric Oxide Synthase