RRC ID 42196
Author Tanaka K, Asanuma M, Ogawa N.
Title Molecular basis of anti-apoptotic effect of immunophilin ligands on hydrogen peroxide-induced apoptosis in human glioma cells.
Journal Neurochem Res
Abstract To clarify the molecular basis of the cytoprotective properties of immunophilin ligands (IPLs), the anti-apoptotic effects of IPLs were determined in human glioma U251 cells. GPI1046 and V10367, non-immunosuppressive IPLs (NI-IPLs), as well as FK506, an immunosuppressive IPL (I-IPL), had cytoprotective effects against hydrogen peroxide (H20O)-induced apoptotic cell death in U251 cells. H2O2 increased both the ratio of bax/bcl-2 and the p53 mRNA expression. However, pre-treatment with FK506 and V10367 significantly prevented any increase in this ratio or p53 mRNA expression. GPI1046 also reduced the ratio of bax/bcl-2 to the normal level. In addition, H2O2 significantly increased activities of all three caspases, caspase-3, caspase-8, and caspase-9, in comparison with non-H2O2 controls. However, FK506 prevented the increase of these caspase activities. On the other hand, it is well-known that glutathione (GSH) and neurotrophic factor (NTF) is related to the induction of apoptosis in neuronal cells. In U251 cells, FK506, GPI1046 and V10367 had GSH-activating and NTF-activating effects. Thus, the immunosuppressive effect is not essential for the cytoprotective properties of IPLs, and IPLs have multiple beneficial properties such as the anti-apoptotic effect, GSH-activating effect, and NTF-activating effect, although the anti-apoptotic effect of NI-IPLs is independent of the regulation of apoptotic activators such as caspase-3.
Volume 29(8)
Pages 1529-36
Published 2004-8-1
DOI 10.1023/b:nere.0000029565.92587.25
PMID 15260130
MeSH Apoptosis / drug effects* Brain Neoplasms Brain-Derived Neurotrophic Factor / metabolism Cell Line, Tumor Cell Survival / drug effects* Glial Cell Line-Derived Neurotrophic Factor Glioma Glutathione / metabolism Humans Hydrogen Peroxide / pharmacology* Immunophilins / physiology* Ligands Nerve Growth Factors / metabolism Pyridines / pharmacology* Pyrrolidines / pharmacology* Tacrolimus / pharmacology*
IF 3.038
Times Cited 20
Human and Animal Cells