Integrated Dissection of Cysteine Oxidative Post-translational Modification Proteome During Cardiac Hypertrophy

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 (CysSO2H), and cysteine sulfonylation (CysSO3H). 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.