title: [Mechanism of opening of mitochondrial permeability transition pore induced by arsenic trioxide].
abstract: OBJECTIVE
  Permeability transition pore (PTP) is central for apoptosis by acting as a good candidate pathway for the release of cytochrome c and apoptosis-induction factors from mitochondria. Arsenite may induce apoptosis via a direct effect on PTP. To characterize the exact mechanism for arsenite to induce PTP opening, the correlations of calcium-induced calcium release from mitochondria (mCICR) to As2O3-induced PTP opening and cytochrome c release from mitochondria were studied.
  
  
  METHODS
  Mitochondria were prepared from Wistar rat livers. The effect of As2O3 on mitochondrial PTP opening was measured with ultraviolet (UV) spectrophotometer. The changes of Ca(2+) concentration were detected with UV spectrophotometer to monitor Ca(2+) -induced Ca(2+) release from mitochondria. Cytochrome c release mediated by Ca(2+) was measured with Western blot.
  
  
  RESULTS
  As2O3 (10 micromol/L) combined with low concentration of Ca(2+) didn't induce PTP opening and cytochrome c release from mitochondria; while As2O3 (10 micromol/L) combined with high concentration of Ca(2+) induced PTP opening and cytochrome c release. When mCICR was inhibited, the effect of As2O3 and Ca(2+) on PTP opening and cytochrome c release was completely inhibited.
  
  
  CONCLUSIONS
  As2O3-induced PTP opening and cytochrome c release depend on mCICR.
authors.affiliation: Instrumental Analysis & Research Center, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Ma
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Qiao
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Tian
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: An-De
authors.initials: AD
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001152:Arsenicals; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010087:Oxides; D045304:Cytochromes c; D000077237:Arsenic Trioxide; D002118:Calcium