Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling

Hyun W. Suh, Seong Man Kang, Ki S. Kwon

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 languageEnglish
Pages (from-to)187-194
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume298
Issue number1-2
DOIs
Publication statusPublished - 2007 Apr 1

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Curcumin
Cell death
Glutamic Acid
Cell Death
Phosphotransferases
JNK Mitogen-Activated Protein Kinases
Toxicity
Cells
Cell Cycle
Cell Cycle Proteins
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Cyclin D1
Extracellular Signal-Regulated MAP Kinases
Neuroprotective Agents
Oxidation-Reduction
Glutathione
Reactive Oxygen Species
Homeostasis
Down-Regulation

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 journalArticle

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