PubMed · 6958129
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L S Durand, G T Rodeheaver, R F Edlich. 1982. Poisoning by pit vipers.. https://pubmed.ncbi.nlm.nih.gov/6958129/
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Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase isolated from bushmaster (Lachesis muta muta) snake venom, which activates the fibrinolytic system in vitro. This study has examined the effect of the plasma proteinase inhibitor alpha2-macroglobulin (alpha2-M) towards LV-PA and compares it with the effect on tissue type plasminogen activator (t-PA). The proteolytic activity of LV-PA alone or previously incubated with human plasminogen (Plg) on the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen (Fg) was completely inhibited by human alpha2-M. However, the synthetic peptides Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost no reduction in rate. At pH 7.4 and 37 degrees C the proteinase (0.15 microM over 15 min) interacted with alpha2-M, and each mole of alpha2-M bound 2 mol of enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that the interaction of alpha2-M with either LV-PA or t-PA preincubated with Plg resulted in the formation of approximately 90 kDa fragments and high molecular mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA) and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic effect can be reduced by alpha2-M in vivo.
Recent studies have implied that GPIb-IX-V as well as functioning as an adhesion receptor may also induce signaling to mediate binding of platelets to damaged vessel wall to prevent bleeding. Reorganization of the cytoskeleton and redistribution of platelet structural proteins and signaling molecules are thought to be important in this early activation process, though the molecular mechanisms remain to be fully defined. In this study, we have used mucetin, a snake venom lectin protein that activates platelets via GPIb, to study the redistribution of GPIb in platelets. In unstimulated platelets, a minor portion of GPIb localized to Triton-insoluble cytoskeleton fractions (TIC). This portion increased considerably after platelet activation by mucetin. We also find increased contents of the FcRgamma chain in TIC. Anti-GPIb antibodies, mocarhagin or cytochalasin D completely inhibited the cytoskeletal translocation. In addition, BAPTA-AM, a cytoplasmic calcium chelator, strongly inhibited this process. On the other hand, inhibitors of alphaIIbbeta3, PLCgamma, PKC, tyrosine kinases, ADP receptor, PI3-kinase or EDTA are effective in preventing GPIb relocation in convulxin- but not in mucetin-activated platelets. We propose that cytoskeletal translocation of GPIb is upstream of alphaIIbbeta3 activation and cross-linking of GPIb is sufficient to induce this event in mucetin-activated platelets.
Snake venom proteins,particularly from the viper and elapid families, have been known to contain a number of platelet active components including what cause platelet aggregation or inhibit platelet aggregation. Some of them have potential clinical usefulness for the treatment of human hemorrhagic or thrombotic disease. Agkistrodon halys pallas belonging to viper family is only growing in China. The aim of this study was to purify a human platelet aggregation inhibitor from venom of Agkistrodon halys pallas and determine its biochemical character. Whether a component could inhibit human platelet aggregation was act as a method to follow the tracks of the protein. Crude venom of Agkistrodon halys pallas was loaded onto a DEAE-Sepharose CL-6B chromatography column could gain 6 peaks. A platelet inhibitor with molecular mass of 65 kD on SDS-PAGE, was purified from peak 2 by Sephadex G-75 gel filtration and SP-Sepharose, Mono Q on FPLC. It could inhibit human platelet aggregation induced by ADP, collagen without activities of phospholipase A2, esterase, fibrinogenolytic. It is concluded that a platelet inhibitor can be isolated and purified from venom of Agkistrodon halys pallas and its inhibition of platelet aggregation is does-dependent.