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- W2000457139 abstract "Abstract We examined the anti-apoptotic effects of immunophilin ligands (IPLs) in U251 cells to clarify the molecular basis of the neuroprotective properties of IPLs. GPI1046 and V10367, which are non-immunosuppressive IPLs, as well as FK506, had neuroprotective effects against hydrogen peroxide (H 2 O 2 )-induced apoptotic cell death in U251 cells. Then, we proceeded to determine the messenger RNA expression of apoptotic activators. H 2 O 2 increased both the ratio of bax/bcl-2 and the p53 mRNA expression. However, pretreatment with FK506 and V10367 prevented significantly the increase of ratio and p53 mRNA. In the ratio of bax/bcl-2, GPI1046 also reduced to the normal level. In addition, we determined the activities of caspase-3, caspase-8, or caspase-9. H 2 O 2 significantly increased all three caspase activities compared with non-H 2 O 2 controls. However, FK506 only prevented the increase of three caspase activities. On the other hand, it is well known that glutathione (GSH) and neurotrophic factor (NTF) are related to the induction of apoptosis in neuronal cells. In U251 cells, three IPLs except for rapamycin had GSH-activating and NTF-activating effect. Thus, the immunosuppressive effect is not essential for the neuroprotective properties of IPLs, and IPLs have multiple beneficial properties such as anti-apoptotic effect, GSH-activating and NTF-activating effect." @default.
- W2000457139 created "2016-06-24" @default.
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- W2000457139 date "2003-06-01" @default.
- W2000457139 modified "2023-09-27" @default.
- W2000457139 title "Immunophilin ameliorates apoptotic neuronal cell death" @default.
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- W2000457139 doi "https://doi.org/10.1016/s0531-5131(03)00070-0" @default.
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