Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol is a major cause of both acute and chronic pancreatitis. Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic inflammation and fibrosis. Herein, we examined the effect of ethanol and acetaldehyde on the activation of transcription factors and mitogen-activated protein (MAP) kinases in PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. PSCs were treated with ethanol and acetaldehyde at clinically relevant concentrations (50 mM and 200 microM, respectively). Ethanol and acetaldehyde activated activator protein-1 but not nuclear factor-kappaB. In addition, they activated three classes of MAP kinases: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 MAP kinase. Ethanol- and acetaldehyde-induced activation of activator protein-1 and MAP kinases was blocked by the antioxidant N-acetyl-cysteine, suggesting a role of oxidative stress in the signal transduction. Ethanol and acetaldehyde induced alpha1(I) procollagen gene expression but did not induce intercellular adhesion molecule-1 and monocyte chemoattractant protein-1. The acetaldehyde-induced increase of alpha1(I) procollagen gene expression was inhibited by the p38 MAP kinase inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580) but not by the MAP kinase inhibitor 2'-amino-3'-methoxyflavone (PD98059). Specific activation of these signal transduction pathways may play a role in the pathogenesis of alcohol-induced pancreatic injury.
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PMID:Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells. 1206 97

Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis and inflammation. However, the signal transduction pathways in PSCs remain largely unknown. We examined the role of p38 mitogen-activated protein (MAP) kinase in the activation of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Activation of p38 MAP kinase was determined by Western blotting using anti-phosphospecific antibody. The effects of two p38 MAP kinase inhibitors, 4-(4-flurophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580) and 4-(4-flurophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole (SB202190), on the parameters of PSC activation, including proliferation, expression of alpha-smooth muscle actin, alpha1(I) procollagen, and prolyl 4-hydroxylase (alpha) genes, and monocyte chemoattractant protein-1 production were evaluated. Interleukin-1beta and platelet-derived growth factor-BB activated p38 MAP kinase. Platelet-derived growth factor-induced PSC proliferation was inhibited by SB203580 and SB202190. These reagents decreased alpha-smooth muscle actin protein expression, and alpha1(I) procollagen and prolyl 4-hydroxylase (alpha) mRNA levels. Treatment with these p38 MAP kinase inhibitors also resulted in inhibition of monocyte chemoattractant protein-1 expression. In addition, SB203580 inhibited spontaneous activation of freshly isolated PSCs in culture on plastic. Thus, inhibition of p38 MAP kinase modulated profibrogenic and proinflammatory actions in PSCs, implying a potential application of p38 MAP kinase inhibitors for the treatment of pancreatic fibrosis and inflammation.
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PMID:Inhibition of p38 mitogen-activated protein kinase blocks activation of rat pancreatic stellate cells. 1249 May 69