title: Suppression of mitochondrial permeability transition pore and induction of lymphoma P388 cell death by cyclosporin A.
abstract: 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.
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Russia. teplova@venus.iteb.serpukhov.su
authors.forename: V
authors.initials: V
authors.lastname: Teplova
authors.forename: Y
authors.initials: Y
authors.lastname: Evtodienko
authors.forename: I
authors.initials: I
authors.lastname: Odinokova
authors.forename: A
authors.initials: A
authors.lastname: Kruglov
authors.forename: A
authors.initials: A
authors.lastname: Kudrjavtsev
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D014812:Vitamin K; C101294:N-methyl-valyl-4-cyclosporin A; D016572:Cyclosporine; C050025:cyclosporin H