These authors contributed equally to this work.
Human glutamylcysteine synthetase protects HEK293 cells against UV-induced cell death through inhibition of c-Jun NH2-terminal kinase
Article first published online: 2 JAN 2013
© The Author(s) Journal compilation © 2005 International Federation for Cell Biology
Cell Biology International
Volume 29, Issue 8, pages 695–702, August 2005
How to Cite
Fan, Y., Wu, D., Jin, L. and Yin, Z. (2005), Human glutamylcysteine synthetase protects HEK293 cells against UV-induced cell death through inhibition of c-Jun NH2-terminal kinase. Cell Biology International, 29: 695–702. doi: 10.1016/j.cellbi.2005.04.006
- Issue published online: 2 JAN 2013
- Article first published online: 2 JAN 2013
- Received 13 October 2004; revised 11 March 2005; accepted 18 April 2005
Human glutamylcysteine ligase catalytic subunit (GCLC) is the rate-limiting enzyme for glutathione synthesis. The heavy subunit possesses all the catalytic activities. UV irradiation (UV-C, 30 J/m2) induced apoptosis in HEK293 cells, but the morphological changes were inhibited significantly by expression of GCLC. MTS assay and flow cytometry results also indicated that GCLC and JNK1APF expression enhanced cellular resistance to UV irradiation. Western blotting showed that irradiation strongly activated the c-Jun NH2-terminal kinases (JNKs) and caspase-3 as well as p38 in HEK293 cells. Interestingly, existing data show that GCLC blocks JNK1 phosphorylation but does not affect p38 phosphorylation. Therefore, overexpression of GCLC protected HEK293 cells against UV irradiation-induced cell death by inhibiting the phosphorylation and activation of JNK1, concomitantly with the inhibition of caspase-3 activation and p21WAF1-luciferase activity downstream of JNK.