Roles of p53, c-Myc, Bcl-2, Bax and caspases in glutamate-induced neuronal apoptosis and the possible neuroprotective mechanism of basic fibroblast growth factor.
By using flow-cytometric analysis, we examined the involvement of p53, c-Myc, Bcl-2 and Bax in the glutamate-induced cell death in cultured cortical neurons. The activities of caspase-1-like and caspase-3-like proteases were also measured after the glutamate treatment. The apoptosis rate of the cells increased after 12 h and 24 h treatment with glutamate. The temporal profile of p53, c-Myc, Bcl-2, Bax expression and caspases activation after glutamate treatment suggest that Bcl-2, c-Myc and caspase-3 play important roles in the excitotoxic neuronal cell death. The down-regulation of Bcl-2 may be an important early stage event, which may cause the activation of caspase-3. c-Myc is also involved in the process of apoptosis though its precise role remains elusive. bFGF exhibited the capability to antagonize the neuronal apoptosis caused by glutamate. The antiapoptotic potential of bFGF may result from its attenuating effect on the down-regulation of Bcl-2 induced by glutamate and, subsequently, blockade of apoptosis cascade. This may provide a possible explanation for its neuroprotective effect against ischemic cell death.
Liu
X
X
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhu
X Z
XZ
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D020169:Caspases