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Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice
Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine β-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein β-hydroxybutyrate is covalently at...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685312/ https://www.ncbi.nlm.nih.gov/pubmed/37805038 http://dx.doi.org/10.1016/j.mcpro.2023.100659 |
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author | Yang, Xuechun Li, Xuehui Yu, Na Yan, Rong Sun, Yan Tang, Congmin Ding, Wenjing Ling, Mingying Song, Yiping Gao, Haiqing Gao, Wenjuan Feng, Junchao Wang, Shaopeng Zhang, Zhen Xing, Yanqiu |
author_facet | Yang, Xuechun Li, Xuehui Yu, Na Yan, Rong Sun, Yan Tang, Congmin Ding, Wenjing Ling, Mingying Song, Yiping Gao, Haiqing Gao, Wenjuan Feng, Junchao Wang, Shaopeng Zhang, Zhen Xing, Yanqiu |
author_sort | Yang, Xuechun |
collection | PubMed |
description | Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine β-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein β-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 β-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications. |
format | Online Article Text |
id | pubmed-10685312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106853122023-11-30 Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice Yang, Xuechun Li, Xuehui Yu, Na Yan, Rong Sun, Yan Tang, Congmin Ding, Wenjing Ling, Mingying Song, Yiping Gao, Haiqing Gao, Wenjuan Feng, Junchao Wang, Shaopeng Zhang, Zhen Xing, Yanqiu Mol Cell Proteomics Research Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine β-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein β-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 β-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications. American Society for Biochemistry and Molecular Biology 2023-10-05 /pmc/articles/PMC10685312/ /pubmed/37805038 http://dx.doi.org/10.1016/j.mcpro.2023.100659 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Yang, Xuechun Li, Xuehui Yu, Na Yan, Rong Sun, Yan Tang, Congmin Ding, Wenjing Ling, Mingying Song, Yiping Gao, Haiqing Gao, Wenjuan Feng, Junchao Wang, Shaopeng Zhang, Zhen Xing, Yanqiu Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title | Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title_full | Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title_fullStr | Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title_full_unstemmed | Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title_short | Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice |
title_sort | proteomics and β-hydroxybutyrylation modification characterization in the hearts of naturally senescent mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685312/ https://www.ncbi.nlm.nih.gov/pubmed/37805038 http://dx.doi.org/10.1016/j.mcpro.2023.100659 |
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