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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Role of p38 MAPK in the Regulation of Apoptosis Signaling Induced by TNF-α in Differentiated PC12 Cells

  • Park, Jung-Gyu (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology) ;
  • Yuk, Youn-Jung (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology) ;
  • Rhim, Hye-When (Biomedical Research Center, Korea Institute of Science and Technology) ;
  • Yi, Seh-Yoon (Department of Applied Chemistry, Dongduk Women's University) ;
  • Yoo, Young-Sook (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
  • Published : 2002.05.31
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Abstract

TNF-$\alpha$ elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-$\alpha$ induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-$\alpha$. TNF-$\alpha$ initiates various signal transduction pathways leading to the activation of the caspase family, NF-${\kappa}B$, Jun N-terminal kinase, and p38 MAPK via the death domain that contains the TNF-$\alpha$ receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-$\alpha$. This implies that the induction of anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-$\alpha$. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-$\alpha$ in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-$\alpha$ slowly increased and lasted several hours in the PC12 cell and DRG neuron. This specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-$\alpha$ in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in resoonse to TNF-$\alpha$ in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.

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References

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