title: Human thioredoxin exerts cardioprotective effect and attenuates reperfusion injury in rats partially via inhibiting apoptosis.
abstract: BACKGROUND
  Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.
  
  
  METHODS
  Purified human thioredoxin was injected into adult Wistar rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondria by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.
  
  
  RESULTS
  Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P < 0.01), notable reduction of myocyte apoptosis (P < 0.01), lower systemic oxidative stress level (P < 0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P < 0.05), and inhibited the activity of caspase-9 (P < 0.05) and caspase-3 (P < 0.01 in mRNA and P < 0.05 at protein level). Meanwhile, human thioredoxin markedly increased bcl-2 expression (P < 0.05).
  
  
  CONCLUSIONS
  These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.
authors.affiliation: Department of Geriatrics, Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Xiao-wei
authors.initials: XW
authors.lastname: Wu
authors.forename: Zong-yan
authors.initials: ZY
authors.lastname: Teng
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Xiu-rong
authors.initials: XR
authors.lastname: Li
authors.forename: Yi-na
authors.initials: YN
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013879:Thioredoxins / Q000494:pharmacology*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013879:Thioredoxins; D053148:Caspase 3