Measuring adriamycin-induced cardiac hemodynamic dysfunction with a proteomics approach.
Adriamycin is a potent antitumor drug that causes severe cardiotoxicity. However, the toxic mechanisms are not clear. We used a proteomics approach to analyze changes in protein profiles after adriamycin-induced changes in hemodynamic factors. Although adriamycin itself did not affect left ventricular developed pressure (LVDP) or left ventricular end diastolic pressure (LVEDP), the drug did enhance susceptibility to ischemia-reperfusion-induced changes in LVDP, LVEDP and heart rate. Adriamycin altered the expression of 52 proteins, primarily energy metabolism and cytoskeleton proteins. Adriamycin decreased the expression of the metabolism-related proteins, ATP synthase, Sdha protein, Triose phosphate isomerase 1 (TPI-1), pyruvate dehydrogenase E1 alpha1, 6-phosphofructokinase, and fructose-1,6-bisphosphatase, as did cytoskeletal proteins, such as actin. Alterations in energy metabolism and subsequent free radical production may affect cytoskeletal protein expression, producing adriamycin-induced changes in cardiac hemodynamics.
Cui
Yan
Y
Department of Pharmacology, Medical School, Chonbuk National University, Jeonju, Republic of Korea.
Piao
Cheng-Shi
CS
Ha
Ki-Chan
KC
Kim
Do-Sung
DS
Lee
Geum-Hwa
GH
Kim
Hae-Kyung
HK
Chae
Soo-Wan
SW
Lee
Yong-Chul
YC
Park
Seoung-Ju
SJ
Yoo
Wan-Hee
WH
Kim
Hyung-Ryong
HR
Chae
Han-Jung
HJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D016277:Ventricular Function, Left / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D011506:Proteins; D004317:Doxorubicin