Physiol. Genomics Information on EB 2010
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Physiol. Genomics 38: 125-137, 2009. First published May 19, 2009; doi:10.1152/physiolgenomics.00033.2009
1094-8341/09 $8.00
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Received 9 February 2009; accepted in final form 12 May 2009.
Physiological Genomics 38:125-137 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Call For Papers: Comparative Genomics

Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart

James D. McCully 1,2, Monoj K. Bhasin 3, Christian Daly 4, Manuel C. Guerrero 3, Simon Dillon 2,3, Towia A. Liberman 2,3, Douglas B. Cowan 2,5, John D. Mably 2,5, Francis X. McGowan 2,5 and Sidney Levitsky 1,2

1 Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
2 Harvard Medical School, Boston, Massachusetts
3 Beth Israel Deaconess Medical Center Genomics Center, Boston, Massachusetts
4 Harvard University Bauer Center for Genomic Research, Boston, Massachusetts
5 Children's Hospital Boston, Boston, Massachusetts

Cardioplegia is used to partially alleviate the effects of surgically induced global ischemia injury; however, the molecular mechanisms involved in this cardioprotection remain to be elucidated. To improve the understanding of the molecular processes modulating the effects of global ischemia and the cardioprotection afforded by cardioplegia, we constructed rabbit heart cDNA libraries and isolated, sequenced, and identified a compendium of nonredundant cDNAs for use in transcriptomic and proteomic analyses. New Zealand White rabbits were used to compare the effects of global ischemia and cardioplegia compared with control (nonischemic) hearts. The effects of RNA and protein synthesis on the cardioprotection afforded by cardioplegia were investigated separately by preperfusion with either {alpha}-amanitin or cycloheximide. Our results demonstrate that cardioplegia partially ameliorates the effects of global ischemia and that the cardioprotection is modulated by RNA- and protein-dependent mechanisms. Transcriptomic and proteomic enrichment analyses indicated that global ischemia downregulated genes/proteins associated with mitochondrial function and energy production, cofactor catabolism, and the generation of precursor metabolites of energy. In contrast, cardioplegia significantly increased differentially expressed genes/proteins associated with the mitochondrion and mitochondrial function and significantly upregulated the biological processes of muscle contraction, involuntary muscle contraction, carboxylic acid and fatty acid catabolic processes, fatty acid β-oxidation, and fatty acid metabolic processes.

mitochondrion; ischemia-reperfusion






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