Abstract

Snakebite is a common occurrence in many parts of the world, paticularly in tropical ares. The venoms of certan snakes, especially the Crotalid family, which includes rattlesnakes, cooperheads, and water mocassins in the United States, causes extensive tissue damage, which in many cases leads to dysfunction or complete loss of extremity. Our objective is to determine the chemical and pharmavological properties of the toxins responsible for hemorrhage and necrosis and the mechanisms of tissue damage on envenomation. Different hemorrhagic toxins and myotoxins will be isolated from snake venoms and their effects on artificial membranes, platelet aggregation, isolated endothelial cells, and sarcoplasmic reticulum will be investigated. In order to establish structure- function relationships of myotoxin a, the toxin wll be modified using several methods and its effect on myonecrotic activity and SR calcium-ATPase activity will be investigated. For the long-term goal, we hope that our research will contribute to the long-range objective of better snakebite treatment, especially n the prevention of tissue damage. Also, by developing the experimental model for this research, we predict their applicability to the study of myodegenerating afflictions and hemorrhagic disorders of man.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37GM015591-25
Application #
3484192
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-06-01
Project End
1997-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
25
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Colorado State University-Fort Collins
Department
Type
Schools of Arts and Sciences
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523

  Publications

Siigur, J; Samel, M; Tonismagi, K et al. (1998) Biochemical characterization of lebetase, a direct-acting fibrinolytic enzyme from Vipera lebetina snake venom. Thromb Res 90:39-49
Datta, G; Tu, A T (1997) Structure and other chemical characterizations of gila toxin, a lethal toxin from lizard venom. J Pept Res 50:443-50
Norris, J W; Fry, R M; Tu, A T (1997) The nucleotide sequence of the translated and untranslated regions of a cDNA for myotoxin a from the venom of prairie rattlesnake (Crotalus viridis viridis). Biochem Biophys Res Commun 230:607-10
Siigur, E; Aaspollu, A; Tu, A T et al. (1996) cDNA cloning and deduced amino acid sequence of fibrinolytic enzyme (lebetase) from Vipera lebetina snake venom. Biochem Biophys Res Commun 224:229-36
Baker, B J; Wongvibulsin, S; Nyborg, J et al. (1995) Nucleotide sequence encoding the snake venom fibrinolytic enzyme atroxase obtained from a Crotalus atrox venom gland cDNA library. Arch Biochem Biophys 317:357-64
Datta, G; Dong, A; Witt, J et al. (1995) Biochemical characterization of basilase, a fibrinolytic enzyme from Crotalus basiliscus basiliscus. Arch Biochem Biophys 317:365-73
Muszkat, K A; Preygerzon, V; Tu, A T (1994) CIDNP study of the aromatic side chain interactions in myotoxin alpha. J Protein Chem 13:333-7
Utaisincharoen, P; Mackessy, S P; Miller, R A et al. (1993) Complete primary structure and biochemical properties of gilatoxin, a serine protease with kallikrein-like and angiotensin-degrading activities. J Biol Chem 268:21975-83
Baker, B; Tu, A T; Middlebrook, J L (1993) Binding of myotoxin a to cultured muscle cells. Toxicon 31:271-84
Obrig, T G; Louise, C B; Moran, T P et al. (1993) Direct cytotoxic effects of hemorrhagic toxins from Crotalus ruber ruber and Crotalus atrox on human vascular endothelial cells, in vitro. Microvasc Res 46:412-6

Showing the most recent 10 out of 18 publications