title: Identification of potential target genes of cardioprotection against ischemia-reperfusion injury by express sequence tags analysis in rat hearts.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) is a powerful mechanism for limiting myocardial infarction during or after ischemia-reperfusion (IR) injury. However, effective target genes and proteins for IPC are unknown. We characterized global changes in gene expression in the heart during IR, and identified effective target genes for IPC.
  
  
  METHODS
  Hearts were isolated from Sprague-Dawley rats under control, IR, and IPC conditions. We generated expressed-sequence-tags (ESTs) for each group and investigated their functions and the major biological processes in which they are involved using the eukaryotic clusters of orthologous groups (KOG) database and bioinformatics analysis tools.
  
  
  RESULTS
  IR modified the expression of 126 genes. Of these, 62 were upregulated, 64 were downregulated, and 77 were found to be effective target genes for IPC. In KOG analysis, most of the genes whose expression was modified were involved in energy production and conversion and the cytoskeleton. A gene-to-gene interaction map revealed that IR modified the expression of genes in four major functional modules: electron transport chain/oxidative phosphorylation; tricarboxylic acid cycle/glucose metabolism/amino acid metabolism; cellular structure and contraction; and gene transcription, translation, and protein folding. At the individual gene level, the genes encoding mitochondrial cytochrome c oxidase subunits 2 and 3 were downregulated, and those encoding the major cytoskeleton components tropomyosin, myosin light chain, myomesin 2, and myosin regulatory light chain 2, as well as the gene encoding the iron-storage protein ferritin, were upregulated, and thus were identified as potential target genes. Real time PCR evaluated expression patterns of three mitochondrial IPC effective genes. Two-dimensional electrophoresis proteomic analyses revealed altered expression of 14 target proteins. The expression patterns of six proteins matched the corresponding EST expression patterns.
  
  
  CONCLUSIONS
  The global profiling of cardiac ischemia-related genes provides the possible mechanisms of IR and IPC and ways of treating IR injury.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Se Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jeong
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Choi
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Ha
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D020224:Expressed Sequence Tags; D015870:Gene Expression; D015723:Gene Library; D019194:Ischemic Preconditioning; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000235:genetics*