Nitric oxide prevents gamma-radiation-induced cell cycle arrest by impairing p53 function in MCF-7 cells |
| |
Authors: | Chazotte-Aubert L Pluquet O Hainaut P Ohshima H |
| |
Affiliation: | Unit of Endogenous Cancer Risk Factors, Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon cedex 08, 69372, France |
| |
Abstract: | We previously reported that nitric oxide (NO) released from S-nitrosoglutathione induces conformational change of the p53 tumor-suppressor protein that impairs its DNA-binding activity in vitro. We now demonstrate that MCF-7 cells preincubated in the presence of 0.5-1 mM S-nitrosoglutathione for 4 h before gamma-irradiation failed to arrest in the G1 phase of the cell cycle, whereas those gamma-irradiated without S-nitrosoglutathione exhibited a normal cell cycle arrest. The S-nitrosoglutathione-treated cells did not express the p53 target gene p21(waf-1) after gamma-irradiation, although p21(waf-1) was strongly expressed in cells irradiated in the absence of S-nitrosoglutathione. These results strongly suggest that NO impairs the function of p53 possibly via conformational change and/or amino acid modifications. On the other hand, cells incubated for 16 h in the presence of 1 mM S-nitrosoglutathione underwent apoptosis with accumulation of the pro-apoptotic protein Bax. This Bax accumulation, however, was shown to occur via a p53-independent pathway. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|