Molecular basis of anti-apoptotic effect of immunophilin ligands on hydrogen peroxide-induced apoptosis in human glioma cells

Ken Ichi Tanaka, Masato Asanuma, Norio Ogawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (H 2O 2)-induced apoptotic cell death in U251 cells. H 2O 2 increased both the ratio of bax/bcl-2 and the p53 mRNA expression. However, pretreatment 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, H 2O 2 significantly increased activities of all three caspases, caspase-3, caspase-8, and caspase-9, in comparison with non-H 2O 2 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.

Original languageEnglish
Pages (from-to)1529-1536
Number of pages8
JournalNeurochemical Research
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Antiapoptosis
  • BDNF
  • FK506
  • GDNF
  • GPI1046
  • V10367
  • caspase
  • glutathione
  • neurotrophic factor
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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