Abstract
Glutamate induces cell death by upsetting the cellular redox homeostasis, termed oxidative glutamate toxicity, in a mouse hippocampal cell line, HT22. Extracellular signal-regulated kinases (ERK) 1/2 are known key players in this process. Here we characterized the roles of both MAP kinases and cell cycle regulators in mediating oxidative glutamate toxicity and the neuroprotective mechanisms of curcumin in HT22 cells. c-Jun N-terminal kinase (JNK) and p38 kinase were activated during the glutamate-induced HT22 cell death, but at a later stage than ERK activation. Treatment with a JNK inhibitor, SP600125, or a p38 kinase inhibitor, SB203580, partly attenuated this cell death. Curcumin, a natural inhibitor of JNK signaling, protected the HT22 cells from glutamate-induced death at nanomolar concentrations more efficiently than SP600125. These doses of curcumin affected neither the level of intracellular glutathione nor the level of reactive oxygen species, but inactivated JNK and p38 significantly. Moreover, curcumin markedly upregulated a cell-cycle inhibitory protein, p21cip1, and downregulated cyclin D1 levels, which might help the cell death prevention. Our results suggest that curcumin has a neuroprotective effect against oxidative glutamate toxicity by inhibiting MAP kinase signaling and influencing cell-cycle regulation.
| Original language | English |
|---|---|
| Pages (from-to) | 187-194 |
| Number of pages | 8 |
| Journal | Molecular and Cellular Biochemistry |
| Volume | 298 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 2007 Apr 1 |
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Keywords
- c-Jun N-terminal kinase
- Cell cycle
- Curcumin
- Glutamate
- Neuroprotection
- p21cip1
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry
- Genetics
- Molecular Biology
Cite this
Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling. / Suh, Hyun W.; Kang, Seong Man; Kwon, Ki S.
In: Molecular and Cellular Biochemistry, Vol. 298, No. 1-2, 01.04.2007, p. 187-194.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling
AU - Suh, Hyun W.
AU - Kang, Seong Man
AU - Kwon, Ki S.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - Glutamate induces cell death by upsetting the cellular redox homeostasis, termed oxidative glutamate toxicity, in a mouse hippocampal cell line, HT22. Extracellular signal-regulated kinases (ERK) 1/2 are known key players in this process. Here we characterized the roles of both MAP kinases and cell cycle regulators in mediating oxidative glutamate toxicity and the neuroprotective mechanisms of curcumin in HT22 cells. c-Jun N-terminal kinase (JNK) and p38 kinase were activated during the glutamate-induced HT22 cell death, but at a later stage than ERK activation. Treatment with a JNK inhibitor, SP600125, or a p38 kinase inhibitor, SB203580, partly attenuated this cell death. Curcumin, a natural inhibitor of JNK signaling, protected the HT22 cells from glutamate-induced death at nanomolar concentrations more efficiently than SP600125. These doses of curcumin affected neither the level of intracellular glutathione nor the level of reactive oxygen species, but inactivated JNK and p38 significantly. Moreover, curcumin markedly upregulated a cell-cycle inhibitory protein, p21cip1, and downregulated cyclin D1 levels, which might help the cell death prevention. Our results suggest that curcumin has a neuroprotective effect against oxidative glutamate toxicity by inhibiting MAP kinase signaling and influencing cell-cycle regulation.
AB - Glutamate induces cell death by upsetting the cellular redox homeostasis, termed oxidative glutamate toxicity, in a mouse hippocampal cell line, HT22. Extracellular signal-regulated kinases (ERK) 1/2 are known key players in this process. Here we characterized the roles of both MAP kinases and cell cycle regulators in mediating oxidative glutamate toxicity and the neuroprotective mechanisms of curcumin in HT22 cells. c-Jun N-terminal kinase (JNK) and p38 kinase were activated during the glutamate-induced HT22 cell death, but at a later stage than ERK activation. Treatment with a JNK inhibitor, SP600125, or a p38 kinase inhibitor, SB203580, partly attenuated this cell death. Curcumin, a natural inhibitor of JNK signaling, protected the HT22 cells from glutamate-induced death at nanomolar concentrations more efficiently than SP600125. These doses of curcumin affected neither the level of intracellular glutathione nor the level of reactive oxygen species, but inactivated JNK and p38 significantly. Moreover, curcumin markedly upregulated a cell-cycle inhibitory protein, p21cip1, and downregulated cyclin D1 levels, which might help the cell death prevention. Our results suggest that curcumin has a neuroprotective effect against oxidative glutamate toxicity by inhibiting MAP kinase signaling and influencing cell-cycle regulation.
KW - c-Jun N-terminal kinase
KW - Cell cycle
KW - Curcumin
KW - Glutamate
KW - Neuroprotection
KW - p21cip1
UR - http://www.scopus.com/inward/record.url?scp=34247281580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247281580&partnerID=8YFLogxK
U2 - 10.1007/s11010-006-9365-6
DO - 10.1007/s11010-006-9365-6
M3 - Article
C2 - 17131042
AN - SCOPUS:34247281580
VL - 298
SP - 187
EP - 194
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -