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. 2009 Nov 26;25(6):361–366. doi: 10.1007/s12264-009-0629-5

Aβ31–35-induced neuronal apoptosis is mediated by JNK-dependent extrinsic apoptosis pathway

JNK 激活的外源性凋亡途径介导Aβ31–35 诱导的神经元凋亡

Ling-Min Li 1, Qing-Hua Liu 1, Jian-Tian Qiao 2, Ce Zhang 2,✉
PMCID: PMC5552508  PMID: 19927172

Abstract

Objective

To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31–35-induced apoptosis of cultured cortical neurons.

Methods

Cultured cortical neurons were treated with Aβ31–35 (25 µmol/L) for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation (p-c-Jun) and Fas ligand (FasL) expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software.

Results

Treatment with Aβ31–35 (25 µmol/L) for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Aβ31–35 could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application (100 nmol/L) could completely abolish Aβ31–35 neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Aβ31–35 treatment, and SP600125 (100 nmol/L) significantly inhibited FasL expression.

Conclusion

JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Aβ31–35-induced apoptosis of cultured neurons.

Keywords: Aβ31–35, neurotoxicity, caspase, JNK pathway

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