Evidence of Hyperacetylation of Mitochondrial Regulatory Proteins in Left Ventricular Myocardium of Dogs with Chronic Heart Failure.

Bibliographic Details
Title: Evidence of Hyperacetylation of Mitochondrial Regulatory Proteins in Left Ventricular Myocardium of Dogs with Chronic Heart Failure.
Authors: Gupta, Ramesh C., Szekely, Kristina, Zhang, Kefei, Lanfear, David E., Sabbah, Hani N.
Source: International Journal of Molecular Sciences; Apr2025, Vol. 26 Issue 8, p3856, 10p
Abstract: Increased acetylation or "hyperacetylation" of mitochondrial (MITO) proteins can lead to abnormalities of the electron transport chain (ETC) and oxidative phosphorylation. In this study we examined the levels of proteins that regulate acetylation. Studies were performed in isolated MITO fractions from left ventricular (LV) myocardium of seven healthy normal (NL) dogs and seven dogs with coronary microembolization-induced heart failure (HF, LV ejection fraction ~35%). Protein levels of drivers of hyperacetylation, namely sirtuin-3 (Sirt-3), a MITO deacetylase, and CD38, a regulator of nicotinamide adenine dinucleotide (NAD+), were measured by Western blotting, and the bands were quantified in densitometric units (du). To assess MITO function, MITO components directly influenced by a hyperacetylation state, namely the protein level of cytophillin-D (CyPD), a regulator of MITO permeability transition pore and MITO Complex-I activity, were also measured. Protein level of Sirt-3 and amount of NAD+ were decreased in HF compared to NL dogs. Protein levels of CD38 and CyPD were increased in HF compared to NL dogs. Complex-I activity was decreased in HF compared to NL dogs. The results support the existence of a protein hyperacetylation state in mitochondria of failing LV myocardium compared to NL. This abnormality can contribute to MITO dysfunction as evidenced by reduced Complex-I activity and opening of MITO permeability pores. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
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ISSN:16616596
DOI:10.3390/ijms26083856
Published in:International Journal of Molecular Sciences
Language:English