[Mechanism of opening of mitochondrial permeability transition pore induced by arsenic trioxide].
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.
Ma
Xiao-Dong
XD
Instrumental Analysis & Research Center, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.
Qiao
Dong-Fang
DF
Tian
Xue-Mei
XM
Yan
Fang
F
Ma
An-De
AD
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
D001152:Arsenicals; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010087:Oxides; D045304:Cytochromes c; D000077237:Arsenic Trioxide; D002118:Calcium