PMID- 16631528
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20131121
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 40
IP  - 8
DP  - 2006 Apr 15
TI  - The superoxide dismutase inhibitor diethyldithiocarbamate has antagonistic 
      effects on apoptosis by triggering both cytochrome c release and caspase 
      inhibition.
PG  - 1377-90
AB  - 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.
FAU - Dumay, Anne
AU  - Dumay A
AD  - Universite de Versailles/St. Quentin-en-Yvelines, CNRS FRE-2445, Laboratoire de 
      Genetique et Biologie cellulaire, Versailles, France.
FAU - Rincheval, Vincent
AU  - Rincheval V
FAU - Trotot, Pascale
AU  - Trotot P
FAU - Mignotte, Bernard
AU  - Mignotte B
FAU - Vayssiere, Jean-Luc
AU  - Vayssiere JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051228
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 9007-43-6 (Cytochromes c)
RN  - 99Z2744345 (Ditiocarb)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - *Caspase Inhibitors
MH  - Caspases/*metabolism
MH  - Cytochromes c/*metabolism
MH  - Ditiocarb/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Oxidation-Reduction/drug effects
MH  - Protein Transport/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Sulfhydryl Compounds/metabolism
MH  - Superoxide Dismutase/*antagonists & inhibitors/metabolism
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2006/04/25 09:00
MHDA- 2006/06/10 09:00
CRDT- 2006/04/25 09:00
PHST- 2005/07/29 00:00 [received]
PHST- 2005/11/24 00:00 [revised]
PHST- 2005/12/07 00:00 [accepted]
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - S0891-5849(05)00737-9 [pii]
AID - 10.1016/j.freeradbiomed.2005.12.005 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2006 Apr 15;40(8):1377-90. doi: 
      10.1016/j.freeradbiomed.2005.12.005. Epub 2005 Dec 28.