Catalytic consumption of nitric oxide by 12/15- lipoxygenase: inhibition of monocyte soluble guanylate cyclase activation

Coffey, Marcus Jonathan, Natarajan, Rama, Chumley, Philip H., Coles, Barbara, Thimmalapura, Pushpa-Rekha, Nowell, Mari Ann, Kühn, Hartmut, Lewis, Malcolm John, Freeman, Bruce A. and O'Donnell, Valerie Bridget ORCID: https://orcid.org/0000-0003-4089-8460 2001. Catalytic consumption of nitric oxide by 12/15- lipoxygenase: inhibition of monocyte soluble guanylate cyclase activation. Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490 98 (14) , pp. 8006-8011. 10.1073/pnas.141136098

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Abstract

12/15-Lipoxygenase (LOX) activity is elevated in vascular diseases associated with impaired nitric oxide (( small middle dot)NO) bioactivity, such as hypertension and atherosclerosis. In this study, primary porcine monocytes expressing 12/15-LOX, rat A10 smooth muscle cells transfected with murine 12/15-LOX, and purified porcine 12/15-LOX all consumed *NO in the presence of lipid substrate. Suppression of LOX diene conjugation by *NO was also found, although the lipid product profile was unchanged. *NO consumption by porcine monocytes was inhibited by the LOX inhibitor, eicosatetraynoic acid. Rates of arachidonate (AA)- or linoleate (LA)-dependent *NO depletion by porcine monocytes (2.68 +/- 0.03 nmol x min(-1) x 10(6) cells(-1) and 1.5 +/- 0.25 nmol x min(-1) x 10(6) cells(-1), respectively) were several-fold greater than rates of *NO generation by cytokine-activated macrophages (0.1-0.2 nmol x min(-1) x 10(6) cells(-1)) and LA-dependent *NO consumption by primary porcine monocytes inhibited *NO activation of soluble guanylate cyclase. These data indicate that catalytic *NO consumption by 12/15-LOX modulates monocyte *NO signaling and suggest that LOXs may contribute to vascular dysfunction not only by the bioactivity of their lipid products, but also by serving as catalytic sinks for *NO in the vasculature.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Uncontrolled Keywords:	arachidonate ; linoleate ; hypertension ; atherosclerosis
Publisher:	National Academy of Sciences
ISSN:	1091-6490
Last Modified:	06 Nov 2024 22:34
URI:	https://orca.cardiff.ac.uk/id/eprint/19

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