Integrated Dissection of Cysteine Oxidative Post-translational Modification Proteome During Cardiac Hypertrophy
Open accessAbstract
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 Ca 2+ 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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Identification of proteoforms (genetic variations, alternatively spliced products, phosphorylation, glycosylation, oxidative and other post-translational modifications) allows cardiovascular disease sub-classification.
“Now, identification of proteoforms (e.g., genetic variations, alternatively spliced products, phosphorylation118, glycosylation119, oxidative120 and other PTMs121) allow CVD sub-classification.”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [120]
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Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment
Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., Olsen, J. V., & Mann, M. (2011) · Journal of Proteome Research · doi:10.1021/pr101065j · Cited by 5,349 · see citing works
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,120 · see citing works
2016 update of the PRIDE database and its related tools
Vizcaíno, J. A., Csordás, A., del‐Toro, N., Dianes, J. A., Griss, J., Lavidas, I., Mayer, G., Pérez‐Riverol, Y., Reisinger, F., Ternent, T., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1145 · Cited by 3,466 · see citing works
The Reactome Pathway Knowledgebase
Fabregat, A., Jupe, S., Matthews, L. R., Sidiropoulos, K., Gillespie, M. E., Garapati, P. V., Haw, R., Jassal, B., Korninger, F., May, B., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1132 · Cited by 2,798 · see citing works
Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics
Boersema, P. J., Raijmakers, R., Lemeer, S., Mohammed, S., & Heck, A. J. R. (2009) · Nature Protocols · doi:10.1038/nprot.2009.21 · Cited by 1,359 · see citing works
The Reactome pathway Knowledgebase
Fabregat, A., Sidiropoulos, K., Garapati, P., Gillespie, M., Hausmann, K., Haw, R., Jassal, B., Jupe, S., Korninger, F., McKay, S., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1351 · Cited by 1,201 · see citing works
Physiological and pathological cardiac hypertrophy
Shimizu, I., & Minamino, T. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.06.001 · Cited by 892 · see citing works
Deutsch, E. W., Csordás, A., Sun, Z., Jarnuczak, A. F., Pérez‐Riverol, Y., Ternent, T., Campbell, D. S., Llinares, M. B., Okuda, S., Kawano, S., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw936 · Cited by 864 · see citing works
2016 update of the PRIDE database and its related tools
Vizcaíno, J. A., Csordás, A., del‐Toro, N., Dianes, J. A., Griss, J., Lavidas, I., Mayer, G., Pérez‐Riverol, Y., Reisinger, F., Ternent, T., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw880 · Cited by 806 · see citing works
The Biotin Switch Method for the Detection of S -Nitrosylated Proteins
Jaffrey, S. R., & Snyder, S. H. (2001) · Science s STKE · doi:10.1126/stke.2001.86.pl1 · Cited by 805 · see citing works
Stable-Isotope Dimethyl Labeling for Quantitative Proteomics
Hsu, J., Huang, S., Chow, N.-H., & Chen, S. (2003) · Analytical Chemistry · doi:10.1021/ac0348625 · Cited by 701 · see citing works
Essential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock
Liu, L., Yan, Y., Zeng, M., Zhang, J., Hanes, M. A., Ahearn, G. S., McMahon, T., Dickfeld, T. L., Marshall, H. E., Que, L. G., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00131-x · Cited by 546 · see citing works
Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure
Sun, H., Olson, K. C., Gao, C., Prosdocimo, D. A., Zhou, M., Wang, Z., Jeyaraj, D., Youn, J. Y., Ren, S. V., Liu, Y., et al. (2016) · Circulation · doi:10.1161/circulationaha.115.020226 · Cited by 544 · see citing works
Reduction of Cysteine Sulfinic Acid by Sulfiredoxin Is Specific to 2-Cys Peroxiredoxins
Woo, H. A., Jeong, W., Chang, T., Park, K. J., Park, S. J., Yang, J. S., & Rhee, S. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400496200 · Cited by 331 · see citing works
Glucose metabolism and cardiac hypertrophy
Kolwicz, S. C., & Tian, R. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr071 · Cited by 302 · see citing works
Stomberski, C. T., Hess, D. T., & Stamler, J. S. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7403 · Cited by 292 · see citing works
Cardiac oxidative stress in acute and chronic isoproterenol-infused rats
Zhang, G., KIMURA, S., Nishiyama, A., Shokoji, T., Rahman, M. M., Yao, L., NAGAI, Y., FUJISAWA, Y., Miyatake, A., & ABE, Y. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.08.013 · Cited by 269 · see citing works
Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress
van der Reest, J., Lilla, S., Zheng, L., Zanivan, S. R., & Gottlieb, E. (2018) · Nature Communications · doi:10.1038/s41467-018-04003-3 · Cited by 267 · see citing works
Chemical methods for mapping cysteine oxidation
Alcock, L. J., Perkins, M. V., & Chalker, J. M. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00607a · Cited by 249 · see citing works
New insights into IGF-1 signaling in the heart
Troncoso, R., Ibarra, C., Vicencio, J. M., Jaimovich, E., & Lavandero, S. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.002 · Cited by 232 · see citing works
From structure to redox: The diverse functional roles of disulfides and implications in disease
Bechtel, T. J., & Weerapana, E. (2017) · PROTEOMICS · doi:10.1002/pmic.201600391 · Cited by 210 · see citing works
Oxidative stress and cardiac hypertrophy: a review
Maulik, S. K., & Kumar, S. (2012) · Toxicology Mechanisms and Methods · doi:10.3109/15376516.2012.666650 · Cited by 202 · see citing works
Murray, C. I., Uhrigshardt, H., O’Meally, R. N., Cole, R. N., & Eyk, J. E. V. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.013441 · Cited by 185 · see citing works
The Biotin Switch Method for the Detection of S-Nitrosylated Proteins
Jaffrey, S. R., & Snyder, S. H. (2001) · Science Signaling · doi:10.1126/scisignal.862001pl1 · Cited by 176 · see citing works
The neXtProt knowledgebase on human proteins: 2017 update
Gaudet, P., Michel, P.-A., Zahn-Zabal, M., Britan, A., Cusin, I., Domagalski, M., Duek, P. D., Gateau, A., Gleizes, A., Hinard, V., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1062 · Cited by 164 · see citing works
Post‐translational modification is essential for catalytic activity of nitrile hydratase
Murakami, T., Nojiri, M., Nakayama, H., Dohmae, N., Takio, K., Odaka, M., Endo, I., Nagamune, T., & Yohda, M. (2000) · Protein Science · doi:10.1110/ps.9.5.1024 · Cited by 156 · see citing works
Andersson, D. C., Fauconnier, J., Yamada, T., Lacampagne, A., Zhang, S., Katz, A., & Westerblad, H. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.202838 · Cited by 137 · see citing works
S-Nitrosylation of Cardiac Ion Channels
González, D. R., Treuer, A. V., Sun, Q.-A., Stamler, J. S., & Hare, J. M. (2009) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181b72c9f · Cited by 137 · see citing works
Redox regulation of cardiac hypertrophy
Sag, C. M., Santos, C. X. C., & Shah, A. M. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.02.002 · Cited by 124 · see citing works
A Review and Current Perspective on Wilson Disease
Patil, M., Sheth, K. A., Krishnamurthy, A. C., et al. (2013) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2013.06.002 · Cited by 123 · see citing works
Qin, F., Siwik, D. A., Lancel, S., Zhang, J., Kuster, G. M., Luptak, I., Wang, L., Tong, X., Kang, Y. J., Cohen, R. A., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000184 · Cited by 122 · see citing works
Wang, J., Pareja, K., Kaiser, C. A., & Sevier, C. S. (2014) · eLife · doi:10.7554/elife.03496 · Cited by 117 · see citing works
Self-citationThiol‐blocking electrophiles interfere with labeling and detection of protein sulfenic acids
Reisz, J. A., Bechtold, E., King, S. B., et al. (2013) · FEBS Journal · doi:10.1111/febs.12535 · Cited by 115 · see citing works
Reduction of Cysteine Sulfinic Acid in Eukaryotic, Typical 2-Cys Peroxiredoxins by Sulfiredoxin
Lowther, W. T., & Haynes, A. C. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3564 · Cited by 106 · see citing works
Differential Regulation of Proteasome Function in Isoproterenol-Induced Cardiac Hypertrophy
Drews, O., Tsukamoto, O., Liem, D. A., et al. (2010) · Circulation Research · doi:10.1161/circresaha.110.222364 · Cited by 106 · see citing works
Fu, Q., & Li, L. (2005) · Analytical Chemistry · doi:10.1021/ac051324e · Cited by 104 · see citing works
Hua, Y., Zhang, Y., & Ren, J. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01307.x · Cited by 98 · see citing works
Protein Glutathionylation in Cardiovascular Diseases
Pastore, A., & Piemonte, F. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141020845 · Cited by 94 · see citing works
Chasing Cysteine Oxidative Modifications
Murray, C. I., & Eyk, J. E. V. (2012) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.111.961425 · Cited by 88 · see citing works
A large dataset of protein dynamics in the mammalian heart proteome
Lau, E., Cao, Q., Ng, D. C. M., Bleakley, B. J., Dincer, T. U., Bot, B. M., Wang, D., Liem, D. A., Lam, M. P. Y., Ge, J., et al. (2016) · Scientific Data · doi:10.1038/sdata.2016.15 · Cited by 85 · see citing works
Self-citationIntegrated omics dissection of proteome dynamics during cardiac remodeling
Lau, E., Cao, Q., Lam, M. P. Y., Wang, J., Ng, D. C. M., Bleakley, B. J., Lee, J. M., Liem, D. A., Wang, D., Hermjakob, H., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02467-3 · Cited by 85 · see citing works
Self-citationMapping Genetic Contributions to Cardiac Pathology Induced by Beta-Adrenergic Stimulation in Mice
Rau, C. D., Wang, J., Avetisyan, R., Romay, M. C., Martin, L., Ren, S. V., Wang, Y., & Lusis, A. J. (2014) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.113.000732 · Cited by 84 · see citing works
Self-citationMonitoring in vivo reversible cysteine oxidation in proteins using ICAT and mass spectrometry
García‐Santamarina, S., Boronat, S., Domènech, A., Ayté, J., Molina, H., & Hidalgo, E. (2014) · Nature Protocols · doi:10.1038/nprot.2014.065 · Cited by 83 · see citing works
Pressure Overload Induces Early Morphological Changes in the Heart
Souders, C. A., Borg, T. K., Banerjee, I., & Baudino, T. A. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.015 · Cited by 82 · see citing works
Systematic Errors in Peptide and Protein Identification and Quantification by Modified Peptides
Bogdanow, B., Zauber, H., & Selbach, M. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.055103 · Cited by 79 · see citing works
Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice
Zhang, G., Ohmori, K., Nagai, Y., Fujisawa, Y., Nishiyama, A., Abe, Y., & Kimura, S. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.01.012 · Cited by 77 · see citing works
Measurement of S -Nitrosylation Occupancy in the Myocardium With Cysteine-Reactive Tandem Mass Tags
Kohr, M. J., Aponte, A. M., Sun, J., Guček, M., Steenbergen, C., & Murphy, E. (2012) · Circulation Research · doi:10.1161/circresaha.112.271320 · Cited by 70 · see citing works
Kohr, M. J., Evangelista, A. M., Ferlito, M., Steenbergen, C., & Murphy, E. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.01.010 · Cited by 69 · see citing works
Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics
Liu, T., Huang, H. H., Wheeler, D., Xu, Y., Wells, J. A., Song, Y. S., & Wiita, A. P. (2017) · Cell Systems · doi:10.1016/j.cels.2017.05.001 · Cited by 66 · see citing works
Hemoglobin S-nitrosylation plays an essential role in cardioprotection
Zhang, R., Hess, D. T., Reynolds, J. D., & Stamler, J. S. (2016) · Journal of Clinical Investigation · doi:10.1172/jci90425 · Cited by 62 · see citing works
A Linear Mixed Model Spline Framework for Analysing Time Course ‘Omics’ Data
Straube, J., Gorse, A., Huang, B. E., & Cao, K. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134540 · Cited by 61 · see citing works
Wang, J., & Sevier, C. S. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.694810 · Cited by 61 · see citing works
Self-citationKramer, P. A., Duan, J., Qian, W.-J., & Marcinek, D. J. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00347 · Cited by 54 · see citing works
Wang, S.-B., Venkatraman, V., Crowgey, E. L., Liu, T., Fu, Z., Holewinski, R., Ranek, M., Kass, D. A., O’Rourke, B., & Van Eyk, J. E. (2018) · Circulation Research · doi:10.1161/circresaha.118.312789 · Cited by 54 · see citing works
Lim, A., Prokaeva, T. B., McComb, M. E., et al. (2003) · Protein Science · doi:10.1110/ps.0349703 · Cited by 49 · see citing works
Arakawa, T., Kawano, Y., Katayama, Y., Nakayama, H., Dohmae, N., Yohda, M., & Odaka, M. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903979s · Cited by 44 · see citing works
Dual Labeling Biotin Switch Assay to Reduce Bias Derived From Different Cysteine Subpopulations
Chung, H. S., Murray, C. I., Venkatraman, V., Crowgey, E. L., Rainer, P. P., Cole, R. N., Bomgarden, R. D., Rogers, J. C., Balkan, W., Hare, J. M., et al. (2015) · Circulation Research · doi:10.1161/circresaha.115.307336 · Cited by 37 · see citing works
Coupling of Antibodies with Biotin
Haugland, R. P., & You, W. W. (1998) · Methods in molecular biology · doi:10.1007/978-1-59259-257-9_17 · Cited by 30 · see citing works
A Classification Scheme for Redox-Based Modifications of Proteins
Forrester, M. T., & Stamler, J. S. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2006-001ed · Cited by 29 · see citing works
Krenek, P., Kmecova, J., Kucerova, D., et al. (2009) · PubMed · doi:10.1093/eurjhf/hfn026 · Cited by 24 · see citing works
Extracting biologically significant patterns from short time series gene expression data
Tchagang, A., Bui, K. V., McGinnis, T., & Benos, P. V. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-255 · Cited by 23 · see citing works
Quantification of Mitochondrial S-Nitrosylation by CysTMT6 Switch Assay
Murray, C. I., Chung, H. S., Uhrigshardt, H., & Eyk, J. E. V. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-386-2_14 · Cited by 18 · see citing works
Gu, L., & Robinson, R. A. S. (2016) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-016-9307-4 · Cited by 18 · see citing works
Coupling of Antibodies With Biotin
Haugland, R. P., & You, W. W. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-579-4_2 · Cited by 17 · see citing works
Bhasi, K., Forrest, A., & Ramanathan, M. K. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti624 · Cited by 15 · see citing works
Molecular Signature of Nitroso–Redox Balance in Idiopathic Dilated Cardiomyopathies
Menazza, S., Aponte, A. M., Sun, J., Guček, M., Steenbergen, C., & Murphy, E. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.115.002251 · Cited by 13 · see citing works
Li, R., Huang, J., & Kast, J. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00133 · Cited by 12 · see citing works
Disrupted Hydrogen-Bond Network and Impaired ATPase Activity in an Hsc70 Cysteine Mutant
O’Donnell, J. P., Marsh, H. M., Sondermann, H., et al. (2018) · Biochemistry · doi:10.1021/acs.biochem.7b01005 · Cited by 11 · see citing works
Seth, D., & Stamler, J. S. (2015) · Circulation Research · doi:10.1161/circresaha.115.307551 · Cited by 9 · see citing works
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A high-stringency blueprint of the human proteome
Adhikari, S., Nice, E. C., Deutsch, E. W., Lane, L., Omenn, G. S., Pennington, S. R., Paik, Y.-K., Overall, C. M., Corrales, F. J., Cristea, I. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19045-9 · Cited by 210 · see citing works
Self-citationOmenn, G. S., Lane, L., Overall, C. M., Corrales, F. J., Schwenk, J. M., Paik, Y.-K., Van Eyk, J. E., Liu, S., Pennington, S., Snyder, M. P., et al. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00434 · Cited by 40 · see citing works
Paik, Y.-K., Overall, C. M., Corrales, F., Deutsch, E. W., Lane, L., & Omenn, G. S. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00885 · Cited by 21 · see citing works
- Authors
- Wang, J., Choi, H., Chung, N. C., Cao, Q., Ng, D. C. M., Mirza, B., Scruggs, S. B., Wang, D., Garlid, A. O., & Ping, P.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Ping, Peipei
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-08-24
- Volume
- 17
- Issue
- 12
- Pages
- 4243-4257
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- PMC
- PMC6650147
- OpenAlex
- W2888623115
- Cited by
- 20
- References
- 70
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R35-HL135772)
- National Institute of General Medical Sciences (U54-GM114833)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cardiac hypertrophy, protein phosphorylation, creatine metabolism, calcium signaling, glucose metabolism
- MeSH terms
- Calcium, Creatine, Cysteine, Glucose, Cardiomegaly, Humans, Oxidation-Reduction, Phosphorylation, Protein Processing, Post-Translational, Time Factors, Proteome
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