[As2O3-induced permeability transition pore opening in mitochondria depends on Ca2+].
OBJECTIVE
To explore the mechanism of arsenite-induced permeability transition pore (PTP) opening and the role of Ca(2+). in As(2)O(3)-induced PTP opening.


METHODS
The mitochondria were prepared from Wistar rat liver and mitochondrial swelling was assessed spectrophotometrically at 540 nm to evaluate PTP opening. The membrane potential of the mitochondria was measured with fluorescence spectrophotometry.


RESULTS
PTP opening was induced with 10 micromol/L As(2)O(3) in the presence of 10 micromol/L Ca(2+), and the absorbance at 540 nm of the mitochondria did not decrease in response to exclusive treatment with 10 micromol/L As(2)O(3), or to 10 micromol/L As(2)O(3) plus 10 micromol/L Ca(2+) treatment with 0.5 mmol/L EGTA pretreatment. Treatment with As(2)O(3) at 0, 5, 10 and 20 micromol/L in the presence of 50, 20, 10 and 5 micromol/L Ca(2+), respectively, resulted in decreased absorbance at 540 nm of the mitochondria.


CONCLUSIONS
Ca(2+) mediates As(2)O(3)-induced PTP opening. As(2)O(3) lowers Ca(2+) threshold necessary for eliciting PTP opening and thereby regulates cell apoptosis.
Qiao
Dong-fang
DF
Instrumental Analysis and Research Center, Southern Medical University, Guangzhou 510515, China. qiaodf@fimmu.com
Ma
An-de
AD
Yan
Fang
F
Wang
Hui-jun
HJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D001152:Arsenicals; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010087:Oxides; D000077237:Arsenic Trioxide; D002118:Calcium