25-Hydroxycholesterol induces mitochondria-dependent apoptosis via activation of glycogen synthase kinase-3β in PC12 cells

Y. K. Choi, Y. S. Kim, I. Y. Choi, S. W. Kim, Won-Ki Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

25-Hydroxycholesterol (25-OH-chol) induces apoptosis in many cell types. The present study investigated the possible involvement of mitochondria-dependent apoptotic signalling molecules in the death of PC12 cells treated with 25-OH-chol. 25-OH-chol increased the production of reactive oxygen species and opened mitochondrial permeability transition pore, resulting in release of cytochrome c and subsequent activation of caspase-9 and -3. 25-OH-chol induced the activation of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β). The JNK inhibitor SP600125 attenuated the activation of caspase-9 and -3 and reduced 25-OH-chol-induced cell death. GSK inhibitors SB415286 and SB216763 significantly down-regulated JNK activity and attenuated the cytotoxicity of 25-hydroxycholesterol. However, SP600125 did not alter the activity of GSK-3β. The results indicate that 25-OH-chol induces cell death via activation of GSK-3β and subsequent up-regulation of JNK. Pharmacological intervention of GSK-3β-JNK-caspase signalling pathway may be useful for the reduction of cytotoxicity of oxysterols.

Original languageEnglish
Pages (from-to)544-553
Number of pages10
JournalFree Radical Research
Volume42
Issue number6
DOIs
Publication statusPublished - 2008 Jun 1

Fingerprint

Glycogen Synthase Kinase 3
Mitochondria
PC12 Cells
Chemical activation
Apoptosis
Phosphotransferases
Caspase 9
Cell death
Cytotoxicity
Caspase 3
Cell Death
JNK Mitogen-Activated Protein Kinases
Caspases
Cytochromes c
25-hydroxycholesterol
hydroxide ion
Reactive Oxygen Species
Up-Regulation
Pharmacology
Molecules

Keywords

  • 25-Hydroxycholesterol
  • Caspase
  • GSK-3β
  • JNK

ASJC Scopus subject areas

  • Biochemistry

Cite this

25-Hydroxycholesterol induces mitochondria-dependent apoptosis via activation of glycogen synthase kinase-3β in PC12 cells. / Choi, Y. K.; Kim, Y. S.; Choi, I. Y.; Kim, S. W.; Kim, Won-Ki.

In: Free Radical Research, Vol. 42, No. 6, 01.06.2008, p. 544-553.

Research output: Contribution to journalArticle

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