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

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

Research output: Contribution to journalArticle

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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

Fingerprint

Cell death
Caspases
Cadmium
Cell Death
Apoptosis
Caspase 3
Assays
Phosphatidylserines
DNA Fragmentation
Rats
Rhodamine 123
Bisbenzimidazole
Caspase 1
Mitochondria
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
Poisons
Annexin A5
DNA
Substrates

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Kim, M. S., Kim, B. J., Woo, H. N., Kim, K., Kim, K. B., Kim, I. K., & Jung, Y. K. (2000). Cadmium induces caspase-mediated cell death: Suppression by Bcl-2. Toxicology, 145(1), 27-37. https://doi.org/10.1016/S0300-483X(99)00176-6
Kim, M. S. ; Kim, B. J. ; Woo, H. N. ; Kim, Kiwoo ; Kim, K. B. ; Kim, I. K. ; Jung, Y. K. / Cadmium induces caspase-mediated cell death : Suppression by Bcl-2. In: Toxicology. 2000 ; Vol. 145, No. 1. pp. 27-37.
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Kim, MS, Kim, BJ, Woo, HN, Kim, K, Kim, KB, Kim, IK & Jung, YK 2000, 'Cadmium induces caspase-mediated cell death: Suppression by Bcl-2', Toxicology, vol. 145, no. 1, pp. 27-37. https://doi.org/10.1016/S0300-483X(99)00176-6

Cadmium induces caspase-mediated cell death : Suppression by Bcl-2. / Kim, M. S.; Kim, B. J.; Woo, H. N.; Kim, Kiwoo; Kim, K. B.; Kim, I. K.; Jung, Y. K.

In: Toxicology, Vol. 145, No. 1, 07.04.2000, p. 27-37.

Research output: Contribution to journalArticle

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T1 - Cadmium induces caspase-mediated cell death

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AU - Kim, M. S.

AU - Kim, B. J.

AU - Woo, H. N.

AU - Kim, Kiwoo

AU - Kim, K. B.

AU - Kim, I. K.

AU - Jung, Y. K.

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N2 - 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.

AB - 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.

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