Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Romanick, Samantha S., Ulrich, Craig, Schlauch, Karen, Hostler, Andrew, Payne, Jordanna, Woolsey, Rebekah, Quilici, David, Feng, Yumei, Ferguson, Bradley S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127670/
https://www.ncbi.nlm.nih.gov/pubmed/30061171
http://dx.doi.org/10.1042/BSR20180721
_version_ 1783353523766820864
author Romanick, Samantha S.
Ulrich, Craig
Schlauch, Karen
Hostler, Andrew
Payne, Jordanna
Woolsey, Rebekah
Quilici, David
Feng, Yumei
Ferguson, Bradley S.
author_facet Romanick, Samantha S.
Ulrich, Craig
Schlauch, Karen
Hostler, Andrew
Payne, Jordanna
Woolsey, Rebekah
Quilici, David
Feng, Yumei
Ferguson, Bradley S.
author_sort Romanick, Samantha S.
collection PubMed
description 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. Based on this, we examined the impact of obesity on protein lysine acetylation in the left ventricle (LV) of male c57BL/6J mice. We reported that obesity significantly increased heart enlargement and fibrosis. Moreover, immunoblot analysis demonstrated that lysine acetylation was markedly altered with obesity and that this phenomenon was cardiac tissue specific. Mass spectral analysis identified 2515 proteins, of which 65 were significantly impacted by obesity. Ingenuity Pathway Analysis® (IPA) further demonstrated that these proteins were involved in metabolic dysfunction and cardiac remodeling. In addition to total protein, 189 proteins were acetylated, 14 of which were significantly impacted by obesity. IPA identified the Cardiovascular Disease Pathway as significantly regulated by obesity. This network included aconitate hydratase 2 (ACO2), and dihydrolipoyl dehydrogenase (DLD), in which acetylation was significantly increased by obesity. These proteins are known to regulate cardiac function yet, the impact for ACO2 and DLD acetylation remains unclear. Combined, these findings suggest a critical role for cardiac acetylation in obesity-mediated remodeling; this has the potential to elucidate novel targets that regulate cardiac pathology.
format Online
Article
Text
id pubmed-6127670
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-61276702018-09-11 Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry Romanick, Samantha S. Ulrich, Craig Schlauch, Karen Hostler, Andrew Payne, Jordanna Woolsey, Rebekah Quilici, David Feng, Yumei Ferguson, Bradley S. Biosci Rep Research Articles 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. Based on this, we examined the impact of obesity on protein lysine acetylation in the left ventricle (LV) of male c57BL/6J mice. We reported that obesity significantly increased heart enlargement and fibrosis. Moreover, immunoblot analysis demonstrated that lysine acetylation was markedly altered with obesity and that this phenomenon was cardiac tissue specific. Mass spectral analysis identified 2515 proteins, of which 65 were significantly impacted by obesity. Ingenuity Pathway Analysis® (IPA) further demonstrated that these proteins were involved in metabolic dysfunction and cardiac remodeling. In addition to total protein, 189 proteins were acetylated, 14 of which were significantly impacted by obesity. IPA identified the Cardiovascular Disease Pathway as significantly regulated by obesity. This network included aconitate hydratase 2 (ACO2), and dihydrolipoyl dehydrogenase (DLD), in which acetylation was significantly increased by obesity. These proteins are known to regulate cardiac function yet, the impact for ACO2 and DLD acetylation remains unclear. Combined, these findings suggest a critical role for cardiac acetylation in obesity-mediated remodeling; this has the potential to elucidate novel targets that regulate cardiac pathology. Portland Press Ltd. 2018-09-07 /pmc/articles/PMC6127670/ /pubmed/30061171 http://dx.doi.org/10.1042/BSR20180721 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Romanick, Samantha S.
Ulrich, Craig
Schlauch, Karen
Hostler, Andrew
Payne, Jordanna
Woolsey, Rebekah
Quilici, David
Feng, Yumei
Ferguson, Bradley S.
Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title_full Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title_fullStr Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title_full_unstemmed Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title_short Obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via TMT-tagged mass spectrometry
title_sort obesity-mediated regulation of cardiac protein acetylation: parallel analysis of total and acetylated proteins via tmt-tagged mass spectrometry
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127670/
https://www.ncbi.nlm.nih.gov/pubmed/30061171
http://dx.doi.org/10.1042/BSR20180721
work_keys_str_mv AT romanicksamanthas obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT ulrichcraig obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT schlauchkaren obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT hostlerandrew obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT paynejordanna obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT woolseyrebekah obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT quilicidavid obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT fengyumei obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry
AT fergusonbradleys obesitymediatedregulationofcardiacproteinacetylationparallelanalysisoftotalandacetylatedproteinsviatmttaggedmassspectrometry