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Cadmium-induced apoptosis in C6 glioma cells: Mediation by caspase 9-activation

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Abstract

The induction of apoptotic cell death by cadmium was investigated in eight mammalian cell lines. Great differences in the cytotoxicity of cadmium were found with different cell lines: Rat C6 glioma cells turned out to be most sensitive with an IC50-value of 0.7 μM, while human A549 adenocarcinoma cells were relatively resistant with an IC50-value of 164 μM CdCl2. The mode of cadmium-induced cellular death was identified to involve apoptotic DNA fragmentation in three cell lines, i.e., in C6 glioma cells, E367 neuroblastoma cells and NIH3T3 fibroblasts. In C6 glioma cells, this process was investigated in detail. Internucleosomal DNA-fragmentation occurred 40 h after application of CdCl2 and was concentration-dependent between 1–100 μM CdCl2, followed by a decrease at higher concentrations due to necrotic processes. Apoptotic chromatin-condensation and nuclear fragmentation was observed 48 h after application of 2.5 μM CdCl2. Furthermore, cadmium (1 μM, 48 h) caused a breakdown of the mitochondrial membrane potential as shown by the decline in mitochondrial uptake of rhodamine 123. Also, we found an activation of caspase 9, a protease known to be activated in apoptotic processes following mitochondrial damage. Besides Cd2+, other toxic heavy metal ions (Hg2+, Pb2+, Ni2+, Fe2+, CrO4 2−, Cu2+ or Co2+) did not induce apoptotic DNA fragmentation in C6 cells. The only exception was Zn2+ which caused apotosis at high concentrations (>150 μM) whereas it protected against cadmium-induced apoptosis at low concentrations (10–50 μM).

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Authors and Affiliations

  1. Department of Biology and Chemistry, University of Bremen, Bremen, Germany

    Wim Wätjen, Monika Cox & Detmar Beyersmann

  2. Department of Physiology and Biochemistry, University of Pisa, Pisa, Italy

    Marta Biagioli

Authors
  1. Wim Wätjen
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  2. Monika Cox
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  3. Marta Biagioli
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  4. Detmar Beyersmann
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Wätjen, W., Cox, M., Biagioli, M. et al. Cadmium-induced apoptosis in C6 glioma cells: Mediation by caspase 9-activation. Biometals 15, 15–25 (2002). https://doi.org/10.1023/A:1013141926228

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