蛋白质组学
赖氨酸
蛋白质组
氧化磷酸化
柠檬酸循环
生物
生物化学
人口
新陈代谢
内科学
细胞生物学
医学
氨基酸
基因
环境卫生
作者
Xuechun Yang,Xuehui Li,Na Yu,Rong Yan,Yue-Li Sun,Congmin Tang,Wenjing Ding,Mingying Ling,Yiping Song,Haiqing Gao,Wenjuan Gao,Junchao Feng,Shaopeng Wang,Zhen Zhang,Yanqiu Xing
标识
DOI:10.1016/j.mcpro.2023.100659
摘要
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 protein modification 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.
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