期刊
JOURNAL OF PROTEOME RESEARCH
卷 17, 期 12, 页码 4243-4257出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.8b00372
关键词
cysteine oxidative modification; cardiac hypertrophy; redox proteomics; computational workflow; cubic spline; biotin switch
资金
- US National Institutes of Health [R35-HL135772, U54-GM114833]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R35HL135772] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [U54GM114833] Funding Source: NIH RePORTER
Cysteine oxidative modification of cellular proteins is crucial for many aspects of cardiac hypertrophy development. However, integrated dissection of multiple types of cysteine oxidative post-translational modifications (O-PTM) of proteomes in cardiac hypertrophy is currently missing. Here we developed a novel discovery platform that encompasses a customized biotin switch-based quantitative proteomics pipeline and an advanced analytic workflow to comprehensively profile the landscape of cysteine O-PTM in an ISO-induced cardiac hypertrophy mouse model. Specifically, we identified a total of 1655 proteins containing 3324 oxidized cysteine sites by at least one of the following three modifications: reversible cysteine O-PTM, cysteine sulfinylation (CysSO(2)H), and cysteine sulfonylation (CysSO(3)H). Analyzing the hypertrophy signatures that are reproducibly discovered from this computational workflow unveiled four biological processes with increased cysteine O-PTM. Among them, protein phosphorylation, creatine metabolism, and response to elevated Ca2+ pathways exhibited an elevation of cysteine O-PTM in early stages, whereas glucose metabolism enzymes were increasingly modified in later stages, illustrating a temporal regulatory map in cardiac hypertrophy. Our cysteine O-PTM platform depicts a dynamic and integrated landscape of the cysteine oxidative proteome, through the extracted molecular signatures, and provides critical mechanistic insights in cardiac hypertrophy. Data are available via ProteomeXchange with identifier PXD010336.
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