title: Redox-proteomic analysis of doxorubicin-induced altered thiol activity in cardiomyocytes.
abstract: Doxorubicin is an anticancer drug used in a wide range of cancer therapies, yet some side effects have been reported. One of these is cardiotoxicity, including cardiomyopathy and ultimately congestive heart failure. This damage to the heart has been shown to result from doxorubicin-induced reactive oxygen species. However, the cellular targets of doxorubicin-induced oxidative damage on cardiomyocytes are largely unknown. For this, a cysteine-labeling-based two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry (MALDI-TOF/TOF MS) were employed to analyze the impact of doxorubicin treatment on the redox regulation in rat cardiomyocytes. This study demonstrated 25 unique protein features that had significantly changed in their thiol reactivity and revealed that doxorubicin-induced cardiotoxicity involves dysregulation of protein folding, translational regulation and cytoskeleton regulation. Our work shows that this combined proteomic strategy provides a rapid method to study the molecular mechanisms of doxorubicin-induced cytotoxicity in the heart. The identified targets may be useful for further evaluation as potential cardiotoxic biomarkers during damage to the heart induced by doxorubicin, as well as possible diagnostic or therapeutic applications.
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, No. 101, Kuang-Fu Road. Sec. 2, Hsinchu 30013, Taiwan.
authors: Szu-Ting
authors: ST
authors: Lin
authors: Hsiu-Chuan
authors: HC
authors: Chou
authors: Yi-Wen
authors: YW
authors: Chen
authors: Hong-Lin
authors: HL
authors: Chan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051338:Cofilin 1 / Q000737:chemistry / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; C495810:CFL1 protein, human; D051338:Cofilin 1; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D010446:Peptide Fragments; D020543:Proteome; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C517938:NME1 protein, human; D003545:Cysteine