title: [Relationship between hypoxia-induced apoptosis and caspases-3 activation, intracellular calcium overload in cardiomyocytes].
abstract: OBJECTIVE
  To explore the effects of hypoxia on Caspases activation in cardiomyocyte and role of intracellular calcium in this event in cardiomyocytes.
  
  
  METHODS
  After hypoxia 0 min, 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, apoptotic cell percentage was determined with Hoechst 33342 straining. Expressions of Caspases-3 mRNA and release of mitochondrial cytochrome c in primary culture of cardiomyocytes were determined by using RT-PCR and Western blotting respectively.
  
  
  RESULTS
  Elevation of Cyt c in cytosol was in accordance with the decline in mitochondrial Cyt c content. Significant increase in Cyt c in cytosol appeared at 12 h post hypoxia and peaked at 24 h while Cyt c in mitochondria could not be detected at 24 h post hypoxia. Hypoxia up-regulated Caspases-3 mRNA expressions beginning at 3 h post hypoxia. Intracellular calcium overload occurred earlier than release of mitochondrial Cyt c and the activation of Caspase-3 during the hypoxic insult. Inhibition of Caspase-3 activation and pretreatment with calcium chelator BAPTA/AM offered a marked protective effect on hypoxia induced cardiomyocyte apoptosis.
  
  
  CONCLUSIONS
  Hypoxia can induce mitochondrion-dependent Caspase-3 activation in cardiomyocytes and therefore leads to cell apoptosis. Increase of intracellular Ca2+ plays an important role in the activation of Caspase-3 and the induction of apoptosis in cardiomyocytes.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Guang-xu
authors.initials: GX
authors.lastname: Zhu
authors.forename: Zheng-ping
authors.initials: ZP
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D015687:Cell Hypoxia; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D002118:Calcium