Abstract
Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38α MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38α MAPK and JNK1 activation. Notexin treatment evoked p38α MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells.
| Original language | English |
|---|---|
| Pages (from-to) | 754-761 |
| Number of pages | 8 |
| Journal | Toxicon |
| Volume | 55 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2010 |
| Externally published | Yes |
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Keywords
- ATF-2
- C-Jun
- Fas
- FasL
- JNK
- Notexin
- P38 MAPK
ASJC Scopus subject areas
- Toxicology
- Medicine(all)
Cite this
Notexin upregulates Fas and FasL protein expression of human neuroblastoma SK-N-SH cells through p38 MAPK/ATF-2 and JNK/c-Jun pathways. / Chen, Ku Chung; Chang, Long Sen.
In: Toxicon, Vol. 55, No. 4, 01.04.2010, p. 754-761.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Notexin upregulates Fas and FasL protein expression of human neuroblastoma SK-N-SH cells through p38 MAPK/ATF-2 and JNK/c-Jun pathways
AU - Chen, Ku Chung
AU - Chang, Long Sen
PY - 2010/4/1
Y1 - 2010/4/1
N2 - Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38α MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38α MAPK and JNK1 activation. Notexin treatment evoked p38α MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells.
AB - Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38α MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38α MAPK and JNK1 activation. Notexin treatment evoked p38α MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells.
KW - ATF-2
KW - C-Jun
KW - Fas
KW - FasL
KW - JNK
KW - Notexin
KW - P38 MAPK
UR - http://www.scopus.com/inward/record.url?scp=77953459538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953459538&partnerID=8YFLogxK
U2 - 10.1016/j.toxicon.2009.11.008
DO - 10.1016/j.toxicon.2009.11.008
M3 - Article
C2 - 19944115
AN - SCOPUS:77953459538
VL - 55
SP - 754
EP - 761
JO - Toxicon
JF - Toxicon
SN - 0041-0101
IS - 4
ER -