Docosahexaenoic acid down-regulates endothelial Nox 4 through a sPLA2 signalling pathway.
We investigated the anti-inflammatory and antioxidant activities of docosahexaenoic acid (DHA) by evaluating its modulation of the two enzymes most involved in vascular inflammation, i.e. endothelial secreted phospholipase A(2) (sPLA(2)) and NADPH oxidase 4 (Nox) 4. Exposure of human aortic endothelial cells (HAECs) to DHA led to its preferential incorporation into outer leaflet phospholipids. Pre-treatment with DHA abolished HAECs stimulation induced by A23187 and Ang II, whereas the effects on IL-1beta treatment were less pronounced. Group V sPLA(2) RNA was similarly modulated by DHA supplementation. In addition, DHA decreased Nox 4 expression and activity; this effect was associated with reduced production of reactive oxygen species. Further, the use of specific inhibitors allowed demonstrating that group V sPLA(2) is involved in the down-regulation of Nox 4 expression and activity by DHA. This interplay is mediated by ERK and PKC.
Richard
Doriane
D
Laboratory of Micronutrients and Cardiovascular Disease, Université Pierre et Marie Curie, Paris 6, France.
Wolf
Claude
C
Barbe
Ullah
U
Kefi
Kaouthar
K
Bausero
Pedro
P
Visioli
Francesco
F
D000804:Angiotensin II / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D053583:Interleukin-1beta; D000804:Angiotensin II; D004281:Docosahexaenoic Acids; D000001:Calcimycin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054497:Phospholipases A2, Secretory