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Article Dans Une Revue Free Radical Biology and Medicine Année : 2006

The superoxide dismutase inhibitor diethyldithiocarbamate has antagonistic effects on apoptosis by triggering both cytochrome c release and caspase inhibition

Résumé

Tumor necrosis factor-alpha (TNF-alpha) and etoposide both trigger a large and rapid production of reactive oxygen species (ROS) in HeLa cells. This occurs before translocations of the proapoptotic Bax and cytochrome c proteins, the loss of mitochondrial membrane potential (DeltaPsim), and apoptosis. We have used diethyldithiocarbamate (DDC), a well-known inhibitor of Cu, Zn superoxide dismutase to study the role of ROS in this system. We report that DDC strongly inhibits caspase activation, loss of DeltaPsim, and cell death induced by TNF-alpha or etoposide. Surprisingly, DDC does not inhibit Bax and cytochrome c translocations. On the contrary, we have observed that DDC can trigger the translocations of these proteins by itself, without altering DeltaPsim. Here, we report that DDC has at least two antagonistic apoptosis regulation functions. First, DDC triggers ROS-dependent Bax and cytochrome c translocations, which are potentially proapoptotic, and second, DDC inhibits caspase activation and activity, loss of DeltaPsim, and cell death, in a ROS-independent manner. Our results suggest an interesting model in which ROS-dependent Bax and cytochrome c translocations can be studied without interference from later apoptotic events.

Dates et versions

hal-04497237 , version 1 (09-03-2024)

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Citer

Anne Dumay, Vincent Rincheval, Pascale Trotot, Bernard Mignotte, Jean-Luc Vayssière. The superoxide dismutase inhibitor diethyldithiocarbamate has antagonistic effects on apoptosis by triggering both cytochrome c release and caspase inhibition. Free Radical Biology and Medicine, 2006, 40 (8), pp.1377-1390. ⟨10.1016/j.freeradbiomed.2005.12.005⟩. ⟨hal-04497237⟩
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