Quantitative Proteomics for Cardiac Biomarker Discovery Using Isoproterenol-Treated Nonhuman Primates

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• 作者：Benben Song ; Yashu Liu ; Toufan Parman ; Shufeng Liu ; Jennifer K. Miller ; Xiaohua Liu ; Mary J. Tanga ; Jon Mirsalis
• 刊名：Journal of Proteome Research
• 出版年：2014
• 出版时间：December 5, 2014
• 年：2014
• 卷：13
• 期：12
• 页码：5909-5917
• 全文大小：333K
• ISSN：1535-3907

文摘

To identify new cardiac biomarkers, a quantitative proteomic analysis has been performed on serum and heart tissue proteins from three species of nonhuman primates following isoproterenol (ISO) treatment. Three serum proteins鈥攕erum amyloid A (SAA), 伪-1-acid glycoprotein (A1AG), and apolipoprotein A-1 (Apo A1)鈥攚ere consistently identified as changed and remained altered 72 h post dose in all three species post ISO treatment, indicating the potential of including these proteins in preclinical or clinical evaluation of drug-induced cardiac injury. Furthermore, proteomic analysis of heart tissue proteins following ISO treatment demonstrated detrimental effects on calcium signaling and energy generation in cardiac myocytes. It is worth noting that cardiac troponins were not identified in serum but were identified as altered in heart tissue lysate along with other cardiac-specific proteins. This strategy for cardiac biomarker discovery by proteomic screening of heart tissue proteins, followed by verification in serum samples using immunoassays or targeted mass spectrometry, could be applied in future biomarker studies.

Keywords:

tandem mass tag; proteomics; cardiotoxicity; serum biomarkers; isoproterenol; Cynomolgus macaque; Rhesus macaque; African green monkey