Document Detail

Cadmium induces caspase-mediated cell death: suppression by Bcl-2.
MedLine Citation:
PMID:  10771129     Owner:  NLM     Status:  MEDLINE    
Apoptosis is a process of active cell death and is characterized by activation of caspases, DNA fragmentation, and biochemical and morphological changes. To better understand apoptosis, we have characterized the dose- and time-dependent toxic effects of cadmium in Rat-1 fibroblasts. Staining of cells with phosphatidylserine (PS)-annexin V, Hoechst 33258 or Rhodamine 123 and Tunel assays showed that incubating cells with 10 microM cadmium induced a form of cell death exhibiting typical characteristics of apoptosis, including cell shrinkage, externalization of PS, loss of mitochondria membrane potential, nuclear condensation and DNA fragmentation. Expression of Bcl-2 or CrmA each suppressed cadmium-induced cell death although Bcl-2 was somewhat more effective than CrmA. In vitro assay of caspase activity carried out using poly(ADP-ribose) polymerase (PARP) as a substrate as well as intracellular caspase assays using a fluorigenic caspase-3 substrate confirmed that caspase-3 is activated in Rat-1 cells undergoing cadmium-induced apoptosis. Both Asp-Glu-Val-Asp-aldehyde (DEVD-cho) and Tyr-Val-Ala-Asp-chloromethylketone (YVAD-cmk), selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. However, the nonselective caspase inhibitor, z-Val-Ala-Asp-floromethylketone (zVAD-fmk), was the most efficacious agent, almost completely blocking cadmium-induced cell death. Taken together, these results demonstrate that as in other forms of apoptosis, caspases play a central role in cadmium-induced cell death.
M S Kim; B J Kim; H N Woo; K W Kim; K B Kim; I K Kim; Y K Jung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology     Volume:  145     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-06-01     Completed Date:  2000-06-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  27-37     Citation Subset:  IM    
Department of Life Science, Kwangju Institute of Science and Technology, 1 Oryong-dong, Puk-gu, Kwangju, South Korea.
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MeSH Terms
Apoptosis / drug effects*
Cadmium / toxicity*
Caspases / physiology*
Cells, Cultured
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Enzyme Activation
Proto-Oncogene Proteins c-bcl-2 / physiology*
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 7440-43-9/Cadmium; EC 3.4.22.-/Caspases

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