Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mouse astrocyte cultures identical to those used in the present study ammonia increases the production of ouabain-like compounds and Na, K-ATPase activity (Kala et al., 2000). Increased activity of Na, K-ATPase could be the result of enhanced production of ouabain-like compounds, since cultured rat astrocytes react to prolonged exposure to a high concentration of ouabain with an upregulation of the Na, K-ATPase alpha(1) isoform (Hosoi et al., 1997). However, unlike astrocytes in brain in vivo and mouse primary cultures, cultured rat astrocytes do not express the astrocyte-specific alpha(2) isoform, which shows a higher affinity for ouabain (EC(50) approximately 0.1 microM) than the alpha(1) isoform (EC(50) approximately 10 microM). In the present study we have investigated (i) effects of ammonia on mRNA and protein expression of alpha(1) and alpha(2) isoforms in primary cultures of mouse astrocytes; (ii) effects of hyperammonia obtained by urease injection on mRNA and protein expression of alpha(1) and alpha(2) isoforms in the brain in vivo; and (iii) effect on observed upregulation of gene expression of AG1478, an inhibitor of the EGF receptor-tyrosine kinase, PP1, an inhibitor of Src, and GM6001, an inhibitor of Zn(2+)-dependent metalloproteinases in the cultured cells. It was established that alpha(2) mRNA and protein expression, but not alpha(1) expression, was upregulated in cultured astrocytes by 1-4 days of exposure to 3 or 5 mM ammonia and that similar upregulation, contrasted by a downregulation of the neuronal alpha(3) subunit occurred in the hyperammonemic brain. Based on the effects of the inhibitors and literature data it is concluded that ammonia activates formation of an endogenous ouabain-like compound, which binds to the Na, K-ATPase, activating Src, which in turn stimulates the receptor-tyrosine kinase of the EGF receptor, leading to activation of the Ras, Raf, MEK pathway and phosphorylation of ERK(1/2), which eventually causes upregulation of alpha(2) gene expression.
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PMID:Increased Na, K-ATPase alpha2 isoform gene expression by ammonia in astrocytes and in brain in vivo. 2044 29

Helicobacter pylori (H. pylori) is a major human pathogen and plays a central role in chronic gastritis and gastric cancer. Since the adhesion of H. pylori to the human gastric epithelium is the initial and critical step of its infection, anti-H. pylori adhesion agents may be effective for the prevention and therapy of H. pylori-associated diseases. CD74 has recently been identified as a new receptor for H. pylori urease, and we have previously reported that several citrus components strongly suppressed CD74 expression in NCI-N87 gastric carcinoma cells. We found in this present study that auraptene (citrus coumarin) disrupted serum starvation-induced extracellular signaling-regulated kinase (ERK) 1/2 activation and attenuated H. pylori adhesion and IL-8 production in a co-culture system. In addition, the knockdown of CD74 expression led to a significant decrease of H. pylori adhesion, but unexpectedly increased IL-8 production. However, PD98059 (a MEK1/2 inhibitor) dramatically down-regulated this cytokine, suggesting MEK/ERK-dependent IL-8 production. Our results suggest that auraptene suppressed H. pylori adhesion and resulting chemokine production by disrupting ERK1/2 activation.
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PMID:Suppression of CD74 expression and Helicobacter pylori adhesion by auraptene targeting serum starvation-activated ERK1/2 in NCI-N87 gastric carcinoma cells. 2046 Jul 32