Dataset Information

Obesity-mediated regulation of the cardiac acetylome

ABSTRACT: Lysine residues undergo diverse and reversible post-translational modifications including acetylation. Acetylation of lysine residues have traditionally been studied as epigenetic modifiers of histone tails within chromatin that provides an important mechanism for regulating gene expression. In the heart, histone acetylation acts as a key regulator of cardiac remodeling and function. However, recent studies have shown that thousands of proteins (~4,500) can be acetylated at multiple acetylation sites (~15,000 sites). These data suggest that the acetylome rivals phosphorylation in prevalence as a post-translational modification. Based on this, we examined the impact of obesity on the regulation of lysine acetylation in the left ventricle of male c57BL/6J mice. We report that obesity contributed to a significant increase in heart enlargement and fibrosis. Of interest, immunoblot analysis demonstrated that lysine acetylation was markedly altered in response to diet-induced obesity and that this phenomena was cardiac tissue specific. Mass spectral analysis was performed in which 3264 proteins were identified in the left ventricle. Of these, 254 proteins were acetylated, 16 of which were significantly impacted by obesity. Ingenuity Pathway Analysis identified the Cardiovascular Disease network as significantly regulated by obesity, 54 of the 254 acetylated proteins impact this pathway. This network includes LIM domain-binding protein 3 (LDB3), aconitate hydratase (ACO2), and dihydrolipoyl dehydrogenase (DLD), which are all significantly impacted by obesity and known to regulate cardiac function. Combined, these findings suggest a critical role for the cardiac acetylome in obesity-mediated remodeling and ultimately have the potential to elucidate novel targets that regulate cardiac pathology.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Craig Ulrich

LAB HEAD: Craig Ulrich

PROVIDER: PXD008385 | Pride | 2018-08-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Ferguson_20161102_no_norm_no_scale.mzML	Mzml
	Ferguson_20161102_no_norm_no_scale.mzid.gz	Mzid
	Ferguson_20161102_no_norm_no_scale.pride.mgf.gz	Mgf
	fr01.raw	Raw
	fr02.raw	Raw

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Publications

Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry.

Romanick Samantha S SS Ulrich Craig C Schlauch Karen K Hostler Andrew A Payne Jordanna J Woolsey Rebekah R Quilici David D Feng Yumei Y Ferguson Bradley S BS

Bioscience reports 20180907 5

Lysine residues undergo diverse and reversible post-translational modifications (PTMs). Lysine acetylation has traditionally been studied in the epigenetic regulation of nucleosomal histones that provides an important mechanism for regulating gene expression. Histone acetylation plays a key role in cardiac remodeling and function. However, recent studies have shown that thousands of proteins can be acetylated at multiple acetylation sites, suggesting the acetylome rivals the kinome as a PTM. Bas ...[more]

PMID: 30061171

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