Opposite role of changes in mitochondrial membrane potential in different apoptotic processes.
We have studied the role of changes in mitochondrial membrane potential (DeltaPsi) in two widely-used models of apoptosis, such as dexamethasone-treated rat thymocytes and U937 human cells treated with tumor necrosis factor-alpha and cycloheximide. To dissipate DeltaPsi, we used low concentrations of valinomycin, unable per se to induce apoptosis, and demonstrated that the decline in DeltaPsi exerts opposite effects in the two models. Indeed, in U937 cells, depolarization of mitochondria increased apoptosis, which decreased in rat thymocytes. This leads to the suggestion that disruption of DeltaPsi plays opposite roles depending on the experimental model. In U937 cells, the drop of DeltaPsi is a possible contributory cause for the apoptotic process; in rat thymocytes, it could be a limiting factor. We propose that these opposite effects could be due to the different ATP requirement of each apoptotic pathway.
Salvioli
S
S
Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia, via Campi 287, 41100, Modena, Italy.
Barbi
C
C
Dobrucki
J
J
Moretti
L
L
Pinti
M
M
Pedrazzi
J
J
Pazienza
T L
TL
Bobyleva
V
V
Franceschi
C
C
Cossarizza
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D014634:Valinomycin / Q000494:pharmacology
D003574:Cytochrome c Group; D007476:Ionophores; D014409:Tumor Necrosis Factor-alpha; D014634:Valinomycin; D003907:Dexamethasone; D000255:Adenosine Triphosphate; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases