Opposing actions of heat shock protein 90 and 70 regulate nicotinamide adenine dinucleotide phosphate oxidase stability and reactive oxygen species production.

ABSTRACT:

Objective

Excessive reactive oxygen species contribute to vascular dysfunction. We have previously shown that heat shock protein (Hsp90) inhibitors potently suppress Nox 1 to 3 and 5, and the goals of this study were to identify how molecular chaperones regulate Nox function.

Methods and results

In vitro, protein expression of Nox 1 to 2, 5 was decreased by Hsp90 inhibitors in multiple cell types (human pulmonary artery endothelial cells, neutrophils, macrophages, and human saphenous vein). In mice treated with Hsp90 inhibitors, Nox1 expression was reduced in lung along with reduced reactive oxygen species from leukocytes. Elevated reactive oxygen species production in obese (db/db) aorta was suppressed by Hsp90 inhibition. Hsp90 inhibitors did not alter Nox5 micro RNA level

SUBMITTER: Chen F 

PROVIDER: S-EPMC3499642 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature