Regulation of the expression of soluble guanylyl cyclase by reactive oxygen species

Gerassimou, C, Kotanidou, Anastasia, Zhou, Zhiping, Ca, Davina, Roussos, Charis and Papapetropoulos, Andreas (2007) Regulation of the expression of soluble guanylyl cyclase by reactive oxygen species. British Journal of Pharmacology, 150 (8). pp. 1084-1091. ISSN 0007-1188

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Abstract

Background and purpose: Superoxide anions produced during vascular disease scavenge nitric oxide (NO), thereby reducing its biological activity. The aim of the present study was to investigate whether reactive oxygen species (ROS) have a direct effect on soluble guanylyl cyclase (sGC) subunit levels and function and to ascertain the mechanism(s) involved.

Experimental approach: Rat aortic smooth muscle cells (RASM) or freshly isolated vessels were exposed to reactive oxygen species (ROS)-generating agents and sGC subunit expression was determined at the mRNA and/or protein level. cGMP accumulation was also determined in RASM exposed to ROS.

Key results: Incubation of smooth muscle cells with H2O2, xanthine/xanthine oxidase (X/XO) or menadione sodium bisulphite (MSB) significantly decreased protein levels of α1 and β1 subunits of sGC and reduced SNP-induced cGMP formation. Similarly, sGC expression was reduced in freshly isolated vessels exposed to ROS-generating agents. The ROS-triggered inhibition of α1 and β1 levels was not blocked by proteasome inhibitors, suggesting that decreased sGC protein was not due to protein degradation through this pathway. Real time RT-PCR analysis demonstrated a 68% reduction in steady state mRNA levels for the α1 subunit following exposure to H2O2. In addition, α1 promoter-driven luciferase activity in RASM decreased by 60% after H2O2 treatment.

Conclusion and implications: We conclude that oxidative stress triggers a decrease in sGC expression and activity that results from reduced sGC steady state mRNA levels. Altered sGC expression is expected to contribute to the changes in vascular tone and remodeling observed in diseases associated with ROS overproduction.

Item Type:	Article
Uncontrolled Keywords:	cGMP; soluble guanylyl cyclase; reactive oxygen species; nitric oxide
Subjects:	B200 Pharmacology, Toxicology and Pharmacy
Department:	Faculties > Health and Life Sciences > Sport, Exercise and Rehabilitation
Depositing User:	Becky Skoyles
Date Deposited:	20 Dec 2017 08:31
Last Modified:	12 Oct 2019 11:47
URI:	http://nrl.northumbria.ac.uk/id/eprint/32916

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