title: Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte.
abstract: Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity.
authors.affiliation: Department of Pathology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Suresh N
authors.initials: SN
authors.lastname: Kumar
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Konorev
authors.forename: Deepika
authors.initials: D
authors.lastname: Aggarwal
authors.forename: Balaraman
authors.initials: B
authors.lastname: Kalyanaraman
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism*; D054715:Cardiotoxins / Q000009:adverse effects / Q000494:pharmacology; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D004317:Doxorubicin