The effect of chronic doxorubicin treatment on mitogen-activated protein kinases and heat stress proteins in rat hearts.
The study has been designed to characterize protein systems involved in the responses of rat hearts to chronic doxorubicin (DOX) treatment. We investigated the influence of DOX on cardiac function, mitogen-activated protein kinases (MAPKs) and heat stress proteins (HSPs). Doxorubicin was administered to rats by intraperitoneal injections over a period of 6 weeks. In control and DOX-treated hearts exposed to 20 min global ischemia and 40 min reperfusion the recovery of contractile function after ischemia/reperfusion (I/R) was determined. The levels and phosphorylation state of proteins in tissue samples were analyzed using specific antibodies. We found an activation of extracellular signal-regulated kinases (ERKs) in rat hearts exposed to DOX treatment and better recovery of contractile function after I/R. Analysis of HSPs showed that DOX induced up-regulation of the levels of HSP60 and down-regulation of HSP70 levels. The levels and/or specific phosphorylation of other studied proteins (p38-MAPK, HSP27, HSP90) were not influenced by DOX. The results point to the possible role of ERKs and some HSPs in mechanisms underlying the response of rat hearts to chronic DOX treatment.
Šimončíková
P
P
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Ravingerová
T
T
Barančík
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic; D018834:Chaperonin 60 / Q000378:metabolism*; D004195:Disease Models, Animal; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D018834:Chaperonin 60; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases