Amyloid beta peptide increases DP5 expression via activation of neutral sphingomyelinase and JNK in oligodendrocytes

Shawei Chen, Jin Moo Lee, Chenbo Zeng, Hong Chen, Chung Y. Hsu, Jan Xu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

There is growing recognition that white matter pathology is a common feature in Alzheimer's disease. We have previously reported that the amyloid beta peptide (Aβ) induces apoptosis in oligodendrocytes (OLG), via activation of neutral sphingomyelinase (nSMase) and resultant generation of ceramide. In the current study, we report that both Aβ and ceramide increased expression of the proapoptotic protein DP5/Hrk (DP5), and release of cytochrome C from mitochondria to cytoplasm in OLGs. We provide evidence that the Jun N-terminal kinase (JNK) signaling pathway mediates Aβ- and ceramide-induced apoptosis: Both Aβ and ceramide activated JNK phosphorylation, and subsequent AP-1 DNA binding activity; JNK siRNA decreased AP-1 DNA binding, DP5 expression and reduced cell death. Furthermore, inhibition of nSMase attenuated Aβ-induced JNK phosphorylation, AP-1 DNA binding activity, DP5 expression, and cytochrome C release. Collectively, these results suggest that Aβ-induced apoptosis involves the sequential activation of nSMase with ceramide generation, JNK activation, AP-1 DNA binding, and DP5 expression.

Original languageEnglish
Pages (from-to)631-640
Number of pages10
JournalJournal of Neurochemistry
Volume97
Issue number3
DOIs
Publication statusPublished - May 2006

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Sphingomyelin Phosphodiesterase
Ceramides
Amyloid beta-Peptides
Oligodendroglia
Transcription Factor AP-1
Phosphotransferases
Chemical activation
Phosphorylation
DNA
Cytochromes
Apoptosis
Mitochondria
Pathology
Cell death
Small Interfering RNA
Alzheimer Disease
Cytoplasm
Cell Death
Proteins

Keywords

  • Amyloid beta peptide
  • Ceramide
  • DP5
  • Jun N-terminal kinase
  • Neutral sphingomyelinase
  • Oligodendrocyte

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Amyloid beta peptide increases DP5 expression via activation of neutral sphingomyelinase and JNK in oligodendrocytes. / Chen, Shawei; Lee, Jin Moo; Zeng, Chenbo; Chen, Hong; Hsu, Chung Y.; Xu, Jan.

In: Journal of Neurochemistry, Vol. 97, No. 3, 05.2006, p. 631-640.

Research output: Contribution to journalArticle

Chen, Shawei ; Lee, Jin Moo ; Zeng, Chenbo ; Chen, Hong ; Hsu, Chung Y. ; Xu, Jan. / Amyloid beta peptide increases DP5 expression via activation of neutral sphingomyelinase and JNK in oligodendrocytes. In: Journal of Neurochemistry. 2006 ; Vol. 97, No. 3. pp. 631-640.
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