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 language | English |
|---|---|
| Pages (from-to) | 1529-1536 |
| Number of pages | 8 |
| Journal | Neurochemical Research |
| Volume | 29 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2004 |
Fingerprint
Keywords
- Antiapoptosis
- BDNF
- caspase
- FK506
- GDNF
- glutathione
- GPI1046
- neurotrophic factor
- oxidative stress
- V10367
ASJC Scopus subject areas
- Neuroscience(all)
- Biochemistry
Cite this
Molecular basis of anti-apoptotic effect of immunophilin ligands on hydrogen peroxide-induced apoptosis in human glioma cells. / Tanaka, Ken Ichi; Asanuma, Masato; Ogawa, Norio.
In: Neurochemical Research, Vol. 29, No. 8, 08.2004, p. 1529-1536.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular basis of anti-apoptotic effect of immunophilin ligands on hydrogen peroxide-induced apoptosis in human glioma cells
AU - Tanaka, Ken Ichi
AU - Asanuma, Masato
AU - Ogawa, Norio
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Antiapoptosis
KW - BDNF
KW - caspase
KW - FK506
KW - GDNF
KW - glutathione
KW - GPI1046
KW - neurotrophic factor
KW - oxidative stress
KW - V10367
UR - http://www.scopus.com/inward/record.url?scp=3042739759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042739759&partnerID=8YFLogxK
U2 - 10.1023/B:NERE.0000029565.92587.25
DO - 10.1023/B:NERE.0000029565.92587.25
M3 - Article
C2 - 15260130
AN - SCOPUS:3042739759
VL - 29
SP - 1529
EP - 1536
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 8
ER -