Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

ABSTRACT:

Background

Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction.

Methods

We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested.

Results

Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are

SUBMITTER: Lee CF 

PROVIDER: S-EPMC5193133 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature