SB203580, a pharmacological inhibitor of p38 MAP kinase transduction pathway activates ERK and JNK MAP kinases in primary cultures of human hepatocytes.

摘要: Mitogen-activated protein kinases (MAPKs) were extensively studied in cancer-derived cell lines; however, studies non-transformed human cells are scarce. In the current paper, we effect of SB203580, a pharmacological inhibitor p38 MAPK, on activation and inhibition MAPK transduction partway primary hepatocytes (in vitro model differentiated cells) comparison with several tumor lines (proliferating non-differentiated model). addition, analyzed SB203580 extracellular-regulated kinase (ERK) c-jun-N-terminal (JNK) pathways both employing antibodies detecting phosphorylated kinases. We show that activates ERK JNK cultures hepatocytes. The levels ERK-P(Thr202/Tyr204), JNK-P(Thr183/Tyr185) c-Jun-P(Ser63/73), target down-stream JNK, increased by SB203580. contrast, activated but not HepG2, HL-60, Saos-2 HaCaT cancer lines. tested, whether effects due to metabolism. Using liquid chromatography/mass spectrometry, found one minor metabolite liver microsomes HepG2 cells. These data imply biotransformation could be responsible for This study is first report activators (sorbitol, anisomycin, EGF) inhibitors observed differential these compounds cells, implying cell-type specificity essential differences between role function MAPKs normal