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

研究成果: 雜誌貢獻文章

33 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)631-640
頁數10
期刊Journal of Neurochemistry
97
發行號3
DOIs
出版狀態已發佈 - 五月 2006

指紋

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

引用此文

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.

於: Journal of Neurochemistry, 卷 97, 編號 3, 05.2006, p. 631-640.

研究成果: 雜誌貢獻文章

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. 於: Journal of Neurochemistry. 2006 ; 卷 97, 編號 3. 頁 631-640.
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