Cadmium induces caspase-mediated cell death: Suppression by Bcl-2

M. S. Kim, B. J. Kim, H. N. Woo, K. W. Kim, K. B. Kim, I. K. Kim, Y. K. Jung

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)

Abstract

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 μM 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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalToxicology
Volume145
Issue number1
DOIs
Publication statusPublished - 2000 Apr 7

Bibliographical note

Funding Information:
We thank J. Yuan for providing Rat-1/Bcl-2 and Rat-1/CrmA cells and N. Spoerel for critical reading of this manuscript. This work was supported by grant from the Korean Ministry of Science and Technology (Star: 97-NQ-07-01-A) and Education (GE: 97–207) (to Y. Jung).

All Science Journal Classification (ASJC) codes

  • Toxicology

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