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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Cobalt Chloride-induced Apoptosis and Extracellular Signal-regulated Protein Kinase Activation in Human Cervical Cancer HeLa Cells

  • Kim, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Kim, Yoon-Suk (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Kim, Tae-Ue (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University)
  • Received : 2003.02.21
  • Accepted : 2003.04.14
  • Published : 2003.09.30
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Abstract

The molecular mechanism of hypoxia-induced apoptosis has not been clearly elucidated. In this study, we investigated the involvement of extracellular signal-regulated protein kinase (ERK 1/2) in hypoxia-induced apoptosis using cobalt chloride in HeLa human cervical cancer cells. The cobalt chloride was used for the induction of hypoxia, and its $IC_{50}$ was $471.4\;{\mu}M$. We demonstrated the DNA fragmentation after incubation with concentrations more than $50\;{\mu}M$ cobalt chloride for 24 h, and also evidenced the morphological changes of the cells undergoing apoptosis with electron microscopy. Next, we examined the signaling pathway of cobalt chloride-induced apoptosis in HeLa cells. ERK1/2 activation occurred 6 and 9 h after treatment with $600\;{\mu}M$ cobalt chloride. Meanwhile, the pretreatment of the MEK 1 inhibitor (PD98059) completely blocked the cobalt chloride-induced ERK 1/2 activation. At the same time, the activated ERK 1/2 translocated into the nucleus and phosphorylated its transcriptional factor, c-Jun. In addition, the pretreatment of PD98059 inhibited the cobalt chloride-induced DNA fragmentation and apoptotic cell death. These results suggest that cobalt chloride is able to induce apoptotic activity in HeLa cells, and its apoptotic mechanism may be associated with signal transduction via ERK 1/2.

Keywords

Acknowledgement

Supported by : Yonsei University

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