Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy.

ABSTRACT:

Rationale

Oxidation of cysteine residues in class II histone deacetylases (HDACs), including HDAC4, causes nuclear exit, thereby inducing cardiac hypertrophy. The cellular source of reactive oxygen species responsible for oxidation of HDAC4 remains unknown.

Objective

We investigated whether nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), a major nicotinamide adenine dinucleotide phosphate oxidase, mediates cysteine oxidation of HDAC4.

Methods and results

Phenylephrine (100 μmol/L), an α1 adrenergic agonist, induced upregulation of Nox4 (1.5-fold; P<0.05) within 5 minutes, accompanied by increases in O(2)(-) (3.5-fold; P<0.01) from the nuclear membrane and nuclear exit of HDAC4 in cardiomyocytes. Knockdown of Nox4, but not Nox2, attenuated O(2)(-) product

SUBMITTER: Matsushima S 

PROVIDER: S-EPMC3574183 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature