Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that angiotensin II (Ang II) stimulates nitric oxide (NO) production in bovine pulmonary artery endothelial cells (BPAECs) by increasing NO synthase (NOS) expression via the type 2 receptor. The purpose of this study was to identify the Ang II-dependent signaling pathway that mediates this increase in endothelial NOS (eNOS). The Ang II-dependent increase in eNOS expression is prevented when BPAECs are pretreated with the tyrosine kinase inhibitors, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine, which also blocked Ang II-dependent mitogen-activated protein kinase (MAPK) kinase/extracellular-regulated protein kinase (MEK)-1 and MAPK phosphorylation, suggesting that Src is upstream of MAPK in this pathway. Transfection of BPAECs with an Src dominant negative mutant cDNA prevented the Ang II-dependent Src activation and increase in eNOS protein expression. PD98059, a MEK-1 inhibitor, prevented the Ang II-dependent phosphorylation of extracellular-regulated protein kinases 1 and 2 and increase in eNOS expression. Neither AG1478, an epidermal growth factor receptor kinase inhibitor, nor AG1295, a platelet derived growth factor receptor kinase inhibitor, had any effect on Ang II-stimulated Src activity, MAPK activation, or eNOS expression. Pertussis toxin prevented the Ang II-dependent increase in Src activity, MAPK activation, and eNOS expression. These data suggest that Ang II stimulates Src tyrosine kinase via a pertussis toxin-sensitive pathway, which in turn activates the MAPK pathway, resulting in increased eNOS protein expression in BPAECs.
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PMID:Src kinase mediates angiotensin II-dependent increase in pulmonary endothelial nitric oxide synthase. 1519 17

This study was designed to evaluate the signaling pathways coupling adenosine A1 receptors and extracellular signal-regulated kinase (ERK) 1 and 2 in human trabecular meshwork (HTM) cells. Studies were conducted using cultures of primary HTM cells and the HTM-3 cell line. Activation of ERK1/2, location of protein kinase C (PKC) isoforms, and matrix metalloproteinase (MMP) secretion were determined by Western blotting. In primary HTM cells and the HTM-3 cell line, administration of the A1 agonist N6-cyclohexyladenosine (CHA) produced a concentration-dependent increase in ERK1/2 activation. This CHA-induced ERK activation was blocked by pretreatment with the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine or pertussis toxin. Transfection with dominant negative N17 Ras produced only a small (31%) decline in CHA-induced ERK activation, and the response was not altered by pretreatment with the Src tyrosine kinase inhibitor, PP2 [3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-D] pyrimidin-4-amine], the phosphoinositide kinase-3 inhibitor, LY-294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], or the A3 receptor antagonist, MRS-1191 [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate]. Administration of CHA also induced the translocation of PKCalpha from the cytosol to the membrane, and pretreatment with the phospholipase C (PLC) inhibitor, U73122 [1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]-hexyl]-1H-pyrrole-2,5-dione], blocked ERK1/2 activation induced by CHA. Transfection of short interfering RNA targeting PKCalpha blocked the CHA-induced ERK1/2 activation and the secretion of MMP-2. These results confirm the existence of functional adenosine A1 receptors in the trabecular meshwork cells. These receptors are coupled to the activation of ERK1/2 through G(i/o) proteins and dependent upon the upstream activation of PLC and PKCalpha. These studies provide evidence that adenosine A1 receptor agonists increase outflow facility through sequential activation of G(i/o) > PLC > PKCalpha > c-Raf > mitogen-activated protein kinase kinase > ERK1/2, leading to secretion of MMP-2.
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PMID:Mechanisms linking adenosine A1 receptors and extracellular signal-regulated kinase 1/2 activation in human trabecular meshwork cells. 1701 37

The biological function of full-length amyloid-beta protein precursor (APP), the precursor of Abeta, is not fully understood. Mounting studies reported that antibody binding to cell surface APP causes neuronal injury. However, the mechanism of cell surface APP mediating neuronal injury remains to be determined. Colocalization of APP with integrin on cell surface leads us to suppose that focal adhesion (FA) related mechanism is involved in surface APP-mediated neuronal injury. In the present study, results demonstrated that primary cultured neurons treated with antibody against APP-N-terminal not only caused neuronal injury and aberrant morphologic changes of neurite, but also induced reaction of FA proteins appearing an acute increase then decrease pattern. Moreover, the elevation of tyrosine phosphorylation of FA proteins including paxillin and focal adhesion kinase (FAK), and down-regulated expression of protein tyrosine phosphatase (PTP1B) induced by APP antibody were prevented by inhibitor of Src protein kinases 4-amino-5-(4-chlorophenyl)-7(t-butyl) pyrazol (3,4-D) pyramide (PP2) and G protein inhibitor pertussis toxin (PTX), implying that Src family kinase and G protein play roles in APP-induced FA signals. In addition, pretreatment with PTX and PP2 was able to suppress APP-antibody induced neuronal injury. Taken together, the results suggest a novel mechanism for APP mediating neuronal injury through deregulating FA signals.
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PMID:Antibody binding to cell surface amyloid precursor protein induces neuronal injury by deregulating the phosphorylation of focal adhesion signaling related proteins. 1976 67