Measuring adriamycin-induced cardiac hemodynamic dysfunction with a proteomics approach.

Abstract

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.

• Authors: Yan Cui, Cheng-Shi Piao, Ki-Chan Ha, Do-Sung Kim, Geum-Hwa Lee, Hae-Kyung Kim, Soo-Wan Chae, Yong-Chul Lee, Seoung-Ju Park, Wan-Hee Yoo, Hyung-Ryong Kim, Han-Jung Chae
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 32 Issue 3 Pg. 376-86 (Sep 2010) ISSN: 1532-2513 [Electronic] England
• PMID: 20105085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Proteins
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (adverse effects, pharmacology)
• Cytoskeleton (drug effects)
• Doxorubicin (adverse effects, pharmacology)
• Energy Metabolism (drug effects)
• Heart (drug effects, physiopathology)
• Hemodynamics (drug effects)
• Male
• Mice
• Myocardial Reperfusion Injury (chemically induced, metabolism, physiopathology)
• Proteins (analysis, metabolism)
• Proteomics
• Ventricular Function, Left (drug effects)