High molecular mass kininogen inhibits metalloproteinases of Bothrops jararaca snake venom.
High molecular mass kininogen (HK) purified from Bothrops jararaca (Bj) plasma was tested on activities of the Bj venom in vivo and in vitro. Results showed that, when incubated with BjHK, the Bj venom presented inhibition on hemorrhagic, edema forming, myotoxic, and coagulant activities. It is well known that metalloproteinases are directly or indirectly involved in these activities. Similarly, human HK inhibits the hemorrhagic effect of the Bj venom as well as hemorrhagic and enzymatic effects of jararhagin, a hemorrhagic metalloproteinase isolated from Bj venom. Complex between HK and jararhagin was not detected by gel filtration. Nevertheless, the inhibitory effect of the hemorrhagic activity of the venom was only partial when HK was pre-incubated with 0.4mM ZnCl(2) or with 0.45mM CaCl(2). These data suggest that the inhibitory effect depends, at least partially, on the competition for ions between kininogen and metalloproteinases of the venom.
de Camargo Gonçalves
Luís Roberto
LR
Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brazil, 1500, 05503-900 São Paulo-SP, Brazil. lrcg@butantan.gov.br
Chudzinski-Tavassi
Ana Marisa
AM
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D017837:Bothrops / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D004487:Edema / Q000188:drug therapy; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D007704:Kininogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D051379:Mice; D008970:Molecular Weight; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D012910:Snake Venoms / Q000737:chemistry / Q000201:enzymology*; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology; D000097146:Bothrops jararaca Venom
D002118:Calcium; D003402:Creatine Kinase; D003435:Crotalid Venoms; D007704:Kininogens; D008666:Metalloendopeptidases; D045726:Metalloproteases; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; D015032:Zinc; D000097146:Bothrops jararaca Venom