Tolerance to nitroglycerin through proteasomal down-regulation of aldehyde dehydrogenase-2 in a genetic mouse model of ascorbate deficiency.

ABSTRACT:

Background and purpose

L-gulonolactone oxidase-deficient (Gulo((-/-))) mice were used to study the effects of ascorbate deficiency on aortic relaxation by nitroglycerin (GTN) with focus on changes in the expression and activity of vascular aldehyde dehydrogenase-2 (ALDH2), which catalyses GTN bioactivation.

Experimental approach

Ascorbate deficiency was induced in Gulo((-/-)) mice by ascorbate deprivation for 4 weeks. Some of the animals were concomitantly treated with the proteasome inhibitor bortezomib and effects compared with ascorbate-supplemented Gulo((-/-)), untreated or nitrate-tolerant wild-type mice. Aortic relaxation of the experimental groups to GTN, ACh and a NO donor was studied. Changes in mRNA and protein expression of vascular ALDH2 were quantified by qPCR a

SUBMITTER: Wolkart G 

PROVIDER: S-EPMC3623057 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature