Downregulation of ERK2 is essential for the inhibition of radiation-induced cell death in HSP25 overexpressed L929 cells
| Autor: | Cho Hn, Cho Ck, Yun Sil Lee, Seon-Jin Lee, Yong J. Lee |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cyclin D
Cyclin A Down-Regulation Gene Expression Apoptosis Biology Transfection Radiation Tolerance Cell Line Mice Cyclin D1 Radioresistance Animals Enzyme Inhibitors Molecular Biology Heat-Shock Proteins Flavonoids Mitogen-Activated Protein Kinase 1 Cyclin-dependent kinase 1 Mitogen-Activated Protein Kinase 3 MEK inhibitor Cell Biology Cell cycle Molecular biology Neoplasm Proteins Cell biology biology.protein Mitogen-Activated Protein Kinases Molecular Chaperones |
| Zdroj: | Cell Death & Differentiation. 9:448-456 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | We previously reported that overexpression of HSP25 delayed cell growth, increased the level of p21(waf), reduced the levels of cyclin D1, cyclin A and cdc2, and induced radioresistance in L929 cells. In this study, we demonstrated that HSP25 induced-radioresistance was abolished by transfection with plasmids containing antisense hsp25 cDNA. Extracellular regulated kinase (ERK) and MAP kinase/ERK kinase (MEK) expressions as well as their activation (phospho-forms) were inhibited by hsp25 overexpression. Furthermore, when control vector transfected cells were treated with PD98059, MEK inhibitor, they became resistant to radiation, suggesting that inhibition of ERK1/2 activities was essential for radioresistance in L929 cells. To confirm the relationship between ERK1/2 and hsp25-mediated radioresistance, ERK1 or ERK2 cDNA was transiently transfected into the hsp25 overexpressed cells and their radioresistance was examined. HSP25-mediated radioresistance was abolished by overexpression of ERK2, but not by overexpression of ERK1. Alteration of cell cycle distribution and cell cycle related protein expressions (cyclin D, cyclin A and cdc2) by hsp25 overexpression were also recovered by ERK2 cDNA transfection. Increase in Bcl-2 protein by hsp25 gene transfection was also reduced by subsequent ERK2 cDNA-transfection. Taken together, these results suggest that downregulation of ERK2 is essential for the inhibition of radiation-induced cell death in HSP25 overexpressed cells. |
| Databáze: | OpenAIRE |
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