Suppression of mitochondrial permeability transition pore and induction of lymphoma P388 cell death by cyclosporin A.
Suppression of the mitochondrial permeability transition pore (PTP) and induction of lymphoma P388 cell death were studied in the presence of cyclosporin A (CsA) and its derivatives. In experiments with permeabilized P388 cells, CsA and its nonimmunosuppressive derivative N-methyl-Val-4-CsA, but not cyclosporin H (CsH), enhanced Ca2+ accumulation in mitochondria and suppressed PTP opening. Moreover, CsA was able either itself to induce or to enhance a prooxidant-induced P388 programmed cell death. Blebbing and formation of apoptotic bodies were among the observed CsA effects. N-Methyl-Val-4-CsA showed similar effects, but CsH had no effect on P388 cell death. These results show that initial-stage P388 tumour cell death is not related to PTP opening but can be the result of PTP closing with a corresponding increase in the formation of reactive oxygen species.
Teplova
V
V
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Russia. teplova@venus.iteb.serpukhov.su
Evtodienko
Y
Y
Odinokova
I
I
Kruglov
A
A
Kudrjavtsev
A
A
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D021961:Cell Membrane Structures / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology
D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D014812:Vitamin K; C101294:N-methyl-valyl-4-cyclosporin A; D016572:Cyclosporine; C050025:cyclosporin H