Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake).

Abstract

Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC50s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin.

• Authors: Elda E Sánchez, Jacob A Galán, William K Russell, Julio G Soto, David H Russell, John C Pérez
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 212 Issue 1 Pg. 59-68 (Apr 01 2006) ISSN: 0041-008X [Print] United States
• PMID: 16084550 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Crotalid Venoms
• Disintegrins
• Platelet Aggregation Inhibitors
• Adenosine Diphosphate
• Gelatinases

Topics

• Adenosine Diphosphate (antagonists & inhibitors, pharmacology)
• Animals
• Chromatography, Gel
• Chromatography, Ion Exchange
• Chromatography, Liquid
• Crotalid Venoms (chemistry, pharmacology)
• Disintegrins (chemistry, isolation & purification, pharmacology)
• Fibrinolysis (drug effects)
• Gelatinases (metabolism)
• Hemorrhage (blood, chemically induced)
• Humans
• In Vitro Techniques
• Mass Spectrometry
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (chemistry, isolation & purification, pharmacology)
• Viperidae