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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalJournal of Cellular Physiology
Volume222
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinases
Neuroblastoma
Up-Regulation
Down-Regulation
p38 Mitogen-Activated Protein Kinases
Chemical activation
Calcium
Depolarization
Small Interfering RNA
Cell death
notexin
Cell Death
Cells
Degradation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Calcium-stimulated mitogen-activated protein kinase activation elicits Bcl-xL downregulation and Bak upregulation in notexin-treated human neuroblastoma SK-N-SH cells. / Chen, Ku Chung; Liu, Wen Hsin; Kao, Pei Hsiu; Chang, Long Sen.

In: Journal of Cellular Physiology, Vol. 222, No. 1, 01.2010, p. 177-186.

Research output: Contribution to journalArticle

@article{3e82378992174f89be5b14dbb76bbc4d,
title = "Calcium-stimulated mitogen-activated protein kinase activation elicits Bcl-xL downregulation and Bak upregulation in notexin-treated human neuroblastoma SK-N-SH cells",
abstract = "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.",
author = "Chen, {Ku Chung} and Liu, {Wen Hsin} and Kao, {Pei Hsiu} and Chang, {Long Sen}",
year = "2010",
month = "1",
doi = "10.1002/jcp.21934",
language = "English",
volume = "222",
pages = "177--186",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Calcium-stimulated mitogen-activated protein kinase activation elicits Bcl-xL downregulation and Bak upregulation in notexin-treated human neuroblastoma SK-N-SH cells

AU - Chen, Ku Chung

AU - Liu, Wen Hsin

AU - Kao, Pei Hsiu

AU - Chang, Long Sen

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=73949096810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949096810&partnerID=8YFLogxK

U2 - 10.1002/jcp.21934

DO - 10.1002/jcp.21934

M3 - Article

C2 - 19780038

AN - SCOPUS:73949096810

VL - 222

SP - 177

EP - 186

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 1

ER -