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 |
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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 |
Keywords
- ATF-2
- C-Jun
- Fas
- FasL
- JNK
- Notexin
- P38 MAPK
ASJC Scopus subject areas
- Toxicology