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

Journal of Neurochemistry
Shawei ChenJan Xu

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 (Abeta) induces apoptosis in oligodendrocytes (OLG), via activation of neutral sphingomyelinase (nSMase) and resultant generation of ceramide. In the current study, we report that both Abeta 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 Abeta- and ceramide-induced apoptosis: Both Abeta 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 Abeta-induced JNK phosphorylation, AP-1 DNA binding activity, DP5 expression, and cytochrome C release. Collectively, these results suggest that Abeta-induced apoptosis involves the sequential activation of nSMase with ceramide generation, JNK activation, AP-1 DNA binding, and DP5 expression.

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Citations

Jan 15, 2014·Molecular Neurobiology·Kinga Czubowicz, Robert Strosznajder
Jan 13, 2012·Neurochemical Research·Charles R Horres, Yusuf A Hannun
Aug 25, 2009·Biochimica Et Biophysica Acta·Ming-Jen HsuChung Y Hsu
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Dec 3, 2021·Journal of Cardiovascular Translational Research·Jinghui SunChenglong Wang

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