Peroxisome proliferators activate growth regulatory pathways largely via peroxisome proliferator-activated receptor alpha-independent mechanisms
| Autor: | Catherine Kaplanski, Brian J. Ledwith, Cindy J. Pauley |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
Male Transcriptional Activation JUNB p38 mitogen-activated protein kinases Peroxisome proliferator-activated receptor Receptors Cytoplasmic and Nuclear Biology Immediate-Early Proteins Rats Sprague-Dawley Animals Dimethyl Sulfoxide RNA Messenger Enzyme Inhibitors Protein kinase A Cells Cultured Cell Line Transformed chemistry.chemical_classification Mitogen-Activated Protein Kinase Kinases Kinase Cell Biology Cell biology Rats Pyrimidines chemistry Cancer research Hepatocytes Phosphorylation Peroxisome Proliferators Signal transduction Mitogen-Activated Protein Kinases Cell Division Signal Transduction Transcription Factors |
| Zdroj: | Cellular signalling. 14(4) |
| ISSN: | 0898-6568 |
| Popis: | Peroxisome proliferators (PPs) induce liver tumors in rodents through an unknown mechanism requiring PP-activated receptor (PPAR) alpha. Since PPs possess growth modulatory activities that may be important to their hepatocarcinogenicity, we aimed at dissociating the activation of growth signaling pathways from the PPARalpha-mediated response induced by PPs in cultured rat primary hepatocytes. Pretreatment with the differentiation-promoting agent dimethylsulfoxide (DMSO) increased PPARalpha mRNA/protein and enhanced the expression of PPARalpha-regulated genes [fatty acyl Co-A oxidase (FACO), cytochrome P450 4A1 (CYP4A1)] induced by PPs. In contrast, DMSO reduced the expression of immediate early genes (IEG) expression (c-myc, c-jun, c-fos, junB, egr-1) and inhibited mitogen-activated protein kinase (MEK) kinase/extracellular signal-regulated kinases (ERKs) and p38 phosphorylation. Furthermore, the inhibitors Tyrphostin and PD98059 dowregulated IEG/ERKs induction and slightly enhanced the FACO/CYP4A1 response induced by the PP WY-14,643. The stimulation of signal transduction pathways by PPs can be dissociated from PPARalpha activation, thus suggesting that PPs could activate growth regulatory pathways largely via PPARalpha-independent mechanisms. |
| Databáze: | OpenAIRE |
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