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)

The mechanism of morphologic change of human cultured umbilical vein endothelial cells (HUVECs) caused by fibrin was investigated. Ancrod, a thrombin-like enzyme, did not cause morphologic alteration of HUVEC by itself at concentrations ranging from 0.01 to 10 U/ml. However, when 0.02 U/ml of ancrod was added to cultured HUVEC monolayers in the presence of citrated plasma, it caused pronounced morphologic change of HUVEC after 6-10 h incubation period. Gly-Pro-Arg-Pro (4 mg/ml), an inhibitor of fibrin polymerization, prevented the morphologic alteration, indicating that the morphologic alteration was caused by the polymerized fibrin. The morphologic change of HUVEC caused by ancrod-generated fibrin was not observed in the presence of an intracellular calcium mobilization inhibitor TMB-8 (50 microM), and the morphologic alteration was also less pronounced with BAPTA(15 microM)-loaded HUVECs and HUVECs pretreated with EGTA (1.2 mM). Ancrod (in Medium 199) itself did not stimulate phosphoinositide breakdown of HUVEC. However, when ancrod was present in plasma, it caused an increase of [3H]IP1 of HUVECs preloaded with [3H]myoinositol. This IP1 increment was inhibited by Gly-Pro-Arg-Pro. The increase of IP1 was significantly inhibited by the pretreatment of monoclonal antibodies 23C6 and 7E3 directed against alpha v beta 3 integrin. Neomycin (1 mM) and pertussis toxin (100 ng/ml), but not aspirin or mepacrine, blocked this enhanced phosphoinositide breakdown. The morphologic change was also prevented by the monoclonal antibodies, 23C6 and 7E3. These results suggest that both intra- and extra-cellular calcium participate in the event of morphologic change of HUVEC caused by ancrod-generated fibrin, and the morphologic change is mediated, at least in part, by fibrin binding to integrin alpha v beta 3 on HUVECs, causing the subsequent activation of the endogenous G-protein coupled phospholipase C.
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PMID:The morphologic change of endothelial cells by ancrod-generated fibrin is triggered by alpha v beta 3 integrin binding and the subsequent activation of a G-protein coupled phospholipase C. 748 43

Ancrod-generated fibrin has been shown to stimulate prostacyclin synthesis of human umbilical vein endothelial cells (Chang et al., 1994, Biochem. Biophys. Res. Commun. 203, 1920). We further investigated its mechanism of action. The increment of 6-keto prostaglandin F1 alpha stimulated by ancrod-generated fibrin was almost completely inhibited when endothelial cells were either pretreated with 50 microM 8-(N,N'-diethylamino)octyl-3,4,5- trimethoxybenzoate (TMB-8) or preloaded with 15 microM 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). 6-Keto prostaglandin F1 alpha production during 2 and 10 h incubation period was also inhibited by 1.2 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid (EGTA) (41 +/- 12 and 53 +/- 17% inhibition, respectively). Further, ancrod-generated fibrin caused a rapid-onset increase in [3h]inositol monophosphate (IP1) formation in endothelial cells. This increase in IP1 was significantly inhibited by 1 mM Gly-Pro-Arg-Pro, 1 mM neomycin or 100 ng/ml pertussis toxin. At the same time, neomycin and pertussis toxin also significantly inhibited 6-keto prostaglandin F1 alpha synthesis of endothelial cells stimulated by ancrod-generated fibrin. Additionally, the increment of IP1 production as well as prostacyclin production were significantly inhibited by monoclonal antibodies directed against alpha v beta 3. These results suggest that intra- and extra-cellular Ca2+ participate in prostacyclin synthesis stimulated by ancrod-generated fibrin. Ancrod-generated fibrin stimulates pertussis toxin-sensitive G-protein regulated phosphoinositide breakdown, which is responsible for prostacyclin synthesis. This augmentation in prostacyclin synthesis and phosphoinositide breakdown caused by ancrod-generated fibrin area, at least in part, mediated by fibrin binding to integrin alpha v beta 3 on endothelial cells.
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PMID:Integrin alpha v beta 3 and phospholipase C regulate prostacyclin formation of endothelial cells caused by ancrod-generated fibrin. 885 Nov 76

Poisonous snakebite wound is a popular disease worldwide. However, the pathogenesis remains unclear. In the present study, a novel metalloproteinase atrahagin in Chinese cobra (Naja atra) snake venom was purified, using heparin-sepharose followed by Superdex 75 gel filtration chromatography. Apart from its alpha-fibrinogenase activity, atrahagin potently activated human colon, lung and tonsil mast cells with the net histamine release being 25.9+/-4.4, 17.0+/-1.9, 13.2+/-3.6%, respectively. Time course studies revealed that the peak histamine release induced by atrahagin occurred at 12, 12 and 8 min following incubation of the enzyme with colon, lung and tonsil mast cells, respectively. The response of mast cells to atrahagin was abolished by preincubation of the cells with metabolic inhibitors or pertussis toxin, and by removal of Ca2+ and Mg2+ from the challenge buffer. In conclusion, activation of human mast cells by atrahagin indicated that the enzyme might contribute to the pathogenesis of snakebite wound.
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PMID:Potent histamine-releasing activity of atrahagin, a novel snake venom metalloproteinase. 1631 Apr 1