Calcium-stimulated mitogen-activated protein kinase activation elicits Bcl-xL downregulation and Bak upregulation in notexin-treated human neuroblastoma SK-N-SH cells

Ku Chung Chen, Wen Hsin Liu, Pei Hsiu Kao, Long Sen Chang

研究成果: 雜誌貢獻文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

Notechis scutatus scutatus notexin induced apoptotic death of SK-N-SH cells accompanied with downregulation of Bcl-xL, upregulation of Bak, mitochondrial depolarization, and ROS generation. Upon exposure to notexin, Ca 2+-mediated JNK and p38 MAPK activation were observed in SK-N-SH cells. Production of ROS was a downstream event followed by Ca 2+-mediated mitochondrial alteration. Notexin-induced cell death, mitochondrial depolarization, and ROS generation were suppressed by SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor). Moreover, phospho-p38 MAPK and phospho-JNK were proved to be involved in Bcl-xL degradation, and overexpression of Bcl-xL attenuated the cytotoxic effect of notexin. Bak upregulation was elicited by p38 MAPK-mediated ATF-2 activation and JNK-mediated c-Jun activation. Suppression of Bak upregulation by ATF-2 siRNA or c-Jun siRNA attenuated notexin-evoked mitochondrial depolarization and rescued viability of notexin-treated cells. Taken together, our data indicate that notexin-induced apoptotic death of SK-N-SH cells is mediated through mitochondrial alteration triggering by Ca 2+-evoked p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways.

原文英語
頁(從 - 到)177-186
頁數10
期刊Journal of Cellular Physiology
222
發行號1
DOIs
出版狀態已發佈 - 一月 2010
對外發佈

ASJC Scopus subject areas

  • 臨床生物化學
  • 細胞生物學
  • 生理學

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