Measuring adriamycin-induced cardiac hemodynamic dysfunction with a proteomics approach

作者:Cui Yan; Piao Cheng Shi; Ha Ki Chan; Kim Do Sung; Lee Geum Hwa; Kim Hae Kyung; Chae Soo Wan; Lee Yong Chul; Park Seoung Ju; Yoo Wan Hee; Kim Hyung Ryong*; Chae Han Jung
来源:Immunopharmacology and Immunotoxicology, 2010, 32(3): 376-386.
DOI:10.3109/08923970903440168

摘要

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.

  • 出版日期2010-9