title: Venom variation in hemostasis of the southern Pacific rattlesnake (Crotalus oreganus helleri): isolation of hellerase.
abstract: Envenomations by the southern Pacific rattlesnake (Crotalus oreganus helleri) are the most common snakebite accidents in southern California. Intraspecies venom variation may lead to unresponsiveness to antivenom therapy. Even in a known species, venom toxins are recognized as diverse in conformity with interpopulational, seasonal, ontogenetic and individual factors. Five venoms of individual C. oreganus helleri located in Riverside and San Bernardino counties of southern California were studied for their variation in their hemostatic activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms presented the highest lethal activity without hemorrhagic activity. In contrast, San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and San Bernardino 1 venoms presented a significant thrombin-like activity. San Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In relation to the fibrinolytic activity, San Bernardino 3 venom was the most active on fibrin plates, which was in turn neutralized by metal chelating inhibitors. These results demonstrate the differences amongst C. oreganus helleri venoms from close localities. A metalloproteinase, hellerase, was purified by anionic and cationic exchange chromatographies from San Bernardino 3 venom. Hellerase exhibited the ability to break fibrin clots in vitro, which can be of biomedically importance in the treatment of heart attacks and strokes.
authors.affiliation: Laboratorio de Fisiopatología, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, Caracas 1020, Venezuela.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Salazar
authors.forename: Belsy
authors.initials: B
authors.lastname: Guerrero
authors.forename: Bruno
authors.initials: B
authors.lastname: Cantu
authors.forename: Esteban
authors.initials: E
authors.lastname: Cantu
authors.forename: Alexis
authors.initials: A
authors.lastname: Rodríguez-Acosta
authors.forename: John C
authors.initials: JC
authors.lastname: Pérez
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Galán
authors.forename: Andy
authors.initials: A
authors.lastname: Tao
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sánchez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002140:California; D002852:Chromatography, Ion Exchange; D003435:Crotalid Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017839:Crotalus; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007928:Lethal Dose 50; D045726:Metalloproteases / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D045726:Metalloproteases; C541254:hellerase, Crotalus oreganus helleri