[Fatty acids regulate NOX activity].
NADPH oxidase (NOX) is a multimeric enzyme including a catalytic unit, gp91(phox), and several regulating subunits: p22(phox), p40(phox), p47(phox), p67(phox). This enzyme, also known as flavocytochrome b(588), is responsible for a deliberate production of superoxyde anion (O2*-). This enzyme, initially described in polynuclear neutrophils (NOX 2), belongs to a complex family of multimeric isoenzymes whose members are present in many cell types. NOXs are generally associated to cell signaling and they seem involved in physiological phenomena (vascular reactivity, proliferation and cellular migration...) as well as in many diseases. Lipids in general and poly unsaturated fatty acids (PUFA) in particular are able to modulate the activity of NOX in many models. With our fibroblastic model, we show that only arachidonic acid (AA) is able to activate the enzyme directly whereas many PUFA are able to induce a production of reactive oxygen species (ERO). Moreover the decrease of ERO production and NOX activity in fibroblasts triggered by PUFA does not depend on SOD activity but the time course of this decrease is associated with the expression of heme oxygenase 1 (HO-1). Besides a regulation by protein subunits, we propose, according to this model, a loop of regulation of NOX activity including a stimulation by lipids associated with an inhibition by HO-1. Thus, lipids, by interaction with phospholipase A2, release arachidonic acid which stimulates NOX, amplifying superoxyde anion production. This oxygen species may induce redox-sensitive gene transcription such as HO-1. Consequently this enzyme inhibits NOX activity and limits superoxyde anion production by heme degradation and CO production.
Rossary
A
A
UF 21455 Stress Oxydant et Vitamines, Fédération de Biochimie, Hôpital E. Herriot, Lyon.
Arab
K
K
Goudable
J
J
Steghens
J-P
JP
D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases