Integration of Cardiac Proteome Biology and Medicine by a Specialized Knowledgebase

Zong, Nobel; Li, Haomin; Li, Hua; Lam, Maggie P. Y.; Jiménez, Rafael C.; Kim, Christina S.; Deng, Ning; Kim, Allen K.; Choi, Jeong H.; Zelaya, Ivette; Liem, David A.; Meyer, David W.; Odeberg, Jacob; Fang, Changming; Lu, Haojie; Xu, Tao; Weiss, James N.; Duan, Huilong; Uhlén, Mathias; Yates, John R.; Apweiler, Rolf; Ge, Junbo; Hermjakob, Henning; Ping, Peipei

doi:10.1161/circresaha.113.301151

Cited by 51 publications

(46 citation statements)

References 28 publications

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“…Proteins were identified from the acquired mass spectra using ProLuCID (38). Protein functional information and gene ontology (GO) entries were queried through NCBI DAVID (43) and COPaKB (44). Protein turnover kinetics was quantified with ProTurn.…”

Section: Methodsmentioning

confidence: 99%

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

et al. 2014

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Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide ( 2 H 2 O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of β-adrenergic-induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to largescale biomolecular investigations of human disease mechanisms with a temporal perspective.

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Section: Methodsmentioning

confidence: 99%

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

et al. 2014

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“…131 Importantly, a complementary resource designed specifically for systems-level analysis in cardiovascular proteomics was introduced recently. 147 Using these repositories, proteomic data can be assessed for extent of categorical representation or statistical enrichment within particular signaling and metabolic pathways, or from Gene Ontology-specific or other algorithm-specific functions, processes, and cellular components (Figure 2). 143,144,148 In more expansive commercial applications, functionality extends to disease-and development-associated functions 140,143 and to upstream analysis for identification of predictive causative agents or cellular processes responsible for observed effects.…”

Section: Pathway Analysismentioning

confidence: 99%

Transformative Impact of Proteomics on Cardiovascular Health and Disease

Lindsey¹,

Mayr²,

Gomes³

et al. 2015

Circulation

142

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Abstract-The year 2014 marked the 20th anniversary of the coining of the term proteomics. The purpose of this scientific statement is to summarize advances over this period that have catalyzed our capacity to address the experimental, translational, and clinical implications of proteomics as applied to cardiovascular health and disease and to evaluate the current status of the field. Key successes that have energized the field are delineated; opportunities for proteomics to drive basic science research, facilitate clinical translation, and establish diagnostic and therapeutic healthcare algorithms are discussed; and challenges that remain to be solved before proteomic technologies can be readily translated from scientific discoveries to meaningful advances in cardiovascular care are addressed. Proteomics is the result of disruptive technologies, namely, mass spectrometry and database searching, which drove protein analysis from 1 protein at a time to protein mixture analyses that enable large-scale analysis of proteins and facilitate paradigm shifts in biological concepts that address important clinical questions. Over the past 20 years, the field of proteomics has matured, yet it is still developing rapidly. The scope of this statement will extend beyond the reaches of a typical review article and offer guidance on the use of next-generation proteomics for future scientific discovery in the basic research laboratory and clinical settings.

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“…The proteasome may be considered as a specialized organelle for targeted degradation of most cellular proteins [5, 6]. These large multi-subunit proteolytic machines are found in the cytosol, both free and attached to the endoplasmic reticulum (ER), and in the nucleus of eukaryotic cells [7].…”

Section: The Proteasomementioning

confidence: 99%

Proteasomal and lysosomal protein degradation and heart disease

Wang

Robbins

2014

Journal of Molecular and Cellular Cardiology

133

145

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Summary In the cell, the proteasome and lysosomes represent the most important proteolytic machineries, responsible for the protein degradation in the ubiquitin-proteasome system (UPS) and autophagy, respectively. Both the UPS and autophagy are essential to protein quality and quantity control. Alterations in cardiac proteasomal and lysosomal degradation are remarkably associated with most heart disease in humans and are implicated in the pathogenesis of congestive heart failure. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteasomal functional insufficiency or lysosomal insufficiency as a major pathogenic factor in the heart. This review article highlights some recent advances in the research into proteasome and lysosome protein degradation in relation to cardiac pathology and examines the emerging evidence for enhancing degradative capacities of the proteasome and/or lysosome as a new therapeutic strategy for heart disease.

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Integration of Cardiac Proteome Biology and Medicine by a Specialized Knowledgebase

Cited by 51 publications

References 28 publications

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

Transformative Impact of Proteomics on Cardiovascular Health and Disease

Proteasomal and lysosomal protein degradation and heart disease

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