PMID- 14575638
OWN - NLM
STAT- MEDLINE
DCOM- 20031118
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 192
IP  - 3
DP  - 2003 Nov 1
TI  - Mitogen activated protein kinases selectively regulate palytoxin-stimulated gene 
      expression in mouse keratinocytes.
PG  - 212-21
AB  - We have been investigating how the novel skin tumor promoter palytoxin transmits 
      signals through mitogen activated protein kinases (MAPKs). Palytoxin activates 
      three major MAPKs, extracellular signal-regulated kinase (ERK), c-Jun N-terminal 
      kinase (JNK), and p38, in a keratinocyte cell line derived from initiated mouse 
      skin (308). We previously showed that palytoxin requires ERK to increase matrix 
      metalloproteinase-13 (MMP-13) gene expression, an enzyme implicated in 
      carcinogenesis. Diverse stimuli require JNK and p38 to increase MMP-13 gene 
      expression, however. We therefore used the JNK and p38 inhibitors SP 600125 and 
      SB 202190, respectively, to investigate the role of these MAPKs in 
      palytoxin-induced MMP-13 gene expression. Surprisingly, palytoxin does not 
      require JNK and p38 to increase MMP-13 gene expression. Accordingly, ERK 
      activation, independent of palytoxin and in the absence of JNK and p38 
      activation, is sufficient to induce MMP-13 gene expression in 308 keratinocytes. 
      Dexamethasone, a synthetic glucocorticoid that inhibits activator protein-1 
      (AP-1), blocked palytoxin-stimulated MMP-13 gene expression. Therefore, the AP-1 
      site present in the promoter of the MMP-13 gene appears to be functional and to 
      play a key role in palytoxin-stimulated gene expression. Previous studies showed 
      that palytoxin simulates an ERK-dependent selective increase in the c-Fos content 
      of AP-1 complexes that bind to the promoter of the MMP-13 gene. JNK and p38 can 
      also modulate c-Fos. Palytoxin does not require JNK or p38 to increase c-Fos 
      binding, however. Altogether, these studies indicate that ERK plays a distinctly 
      essential role in transmitting palytoxin-stimulated signals to specific nuclear 
      targets in keratinocytes derived from initiated mouse skin.
FAU - Zeliadt, Nicholette A
AU  - Zeliadt NA
AD  - Division of Environmental and Occupational Health, School of Public Health, 
      University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Warmka, Janel K
AU  - Warmka JK
FAU - Wattenberg, Elizabeth V
AU  - Wattenberg EV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Acrylamides)
RN  - 0 (Anthracenes)
RN  - 0 (Cnidarian Venoms)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, mouse)
RN  - OQ17NC0MOV (palytoxin)
RN  - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole)
SB  - IM
MH  - *Acrylamides/toxicity
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Cell Line, Transformed
MH  - *Cnidarian Venoms/toxicity
MH  - Collagenases/biosynthesis/*genetics
MH  - Dexamethasone/pharmacology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression
MH  - Imidazoles/pharmacology
MH  - Keratinocytes/drug effects/*enzymology
MH  - Matrix Metalloproteinase 13
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology
MH  - Pyridines/pharmacology
MH  - Signal Transduction
EDAT- 2003/10/25 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/10/25 05:00
PHST- 2003/10/25 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/10/25 05:00 [entrez]
AID - S0041008X03002989 [pii]
AID - 10.1016/s0041-008x(03)00298-9 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2003 Nov 1;192(3):212-21. doi: 
      10.1016/s0041-008x(03)00298-9.