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Property "Has-20abstract" (as page type) with input value "The-20opening-20of-20the-20permeability-20transition-20pore-20(PTP)-20in-20mitochondria-20plays-20a-20critical-20role-20in-20the-20pathogenesis-20of-20numerous-20diseases.-20Mitochondrial-20matrix-20pyridine-20nucleotides-20are-20potent-20regulators-20of-20the-20PTP,-20but-20the-20role-20of-20extramitochondrial-20nucleotides-20is-20unclear.-0A-0AThe-20PTP-20opening-20was-20explored-20in-20isolated-20mitochondria-20and-20mitochondria-20in-20permeabilized-20differentiated-20and-20undifferentiated-20cells-20in-20the-20presence-20of-20added-20NAD(P)(H)-20in-20combination-20with-20Mg-3Csup-3E2+-3C-2Fsup-3E,-20adenine-20nucleotides-20(AN),-20and-20the-20inhibitors-20of-20AN-20translocase-20(ANT),-20voltage-2Ddependent-20anion-20channel-20(VDAC),-20and-20cyclophilin-20D.-0A-0AAdded-20NAD(H)-20and-20AN,-20but-20not-20NADP(H),-20inhibited-20the-20PTP-20opening-20with-20comparable-20potency.-20PTP-20suppression-20required-20neither-20NAD(H)-20oxidation-20nor-20reduction.-20The-20protective-20effects-20of-20NAD(H)-20and-20cyclosporin-20A-20were-20synergistic,-20and-20the-20effects-20of-20NAD(H)-20and-20millimolar-20AN-20were-20additive.-20The-20conformation-2Dspecific-20ANT-20inhibitors-20were-20unable-20to-20cancel-20the-20protective-20effect-20of-20NADH-20even-20under-20total-20ANT-20inhibition.-20Besides,-20NAD(H)-20activated-20the-20efflux-20of-20mitochondrial-20AN-20via-20ANT.-20VDAC-20ligand-20(Mg-3Csup-3E2+-3C-2Fsup-3E)-20and-20blockers-20(G3139-20and-204,4'-2Ddiisothiocyano-2D2,2'-2Dstilbenedisulfonic-20acid)-20potentiated-20and-20attenuated-20the-20protective-20effect-20of-20NAD(H),-20respectively.-20However,-20in-20embryonic-20and-20cancer-20(undifferentiated)-20cells,-20in-20contrast-20to-20isolated-20differentiated-20hepatocytes-20and-20cardiocytes,-20the-20suppression-20of-20PTP-20opening-20by-20NADH-20was-20negligible-20though-20all-20cells-20tested-20possessed-20a-20full-20set-20of-20VDAC-20isoforms.-0A-0AThe-20study-20revealed-20a-20novel-20mechanism-20of-20PTP-20regulation-20by-20external-20(cytosolic)-20NAD(H)-20through-20the-20allosteric-20site-20in-20the-20OM-20or-20the-20intermembrane-20space.-0A-0AThe-20mechanism-20might-20contribute-20to-20the-20resistance-20of-20differentiated-20cells-20under-20different-20pathological-20conditions-20including-20ischemia-2Freperfusion.-0A-0A-3Csmall-3ECopyright-20©-202019.-20Published-20by-20Elsevier-20B.V.-3C-2Fsmall-3E" contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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