| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Hemorrhagic snake venom induces apoptosis in vascular endothelial cells. In previous investigation, we reported the purification of a vascular apotosis-inducing protein (VAP) from Crotalus atrox.
In this investigation, the cDNA cloning of Vascular apotosis-inducing Proteins (VAPs) have been accomplished. The deduced amino acid sequences of VAP1, VAP2, and HV1 consist of 610, 609, and 612 amino acids. The cDNA-predicted amino acid sequences are highly similar in each other, and are multidomain molecules composed of an N-terminal domain, a metalloproteinase domain, a disintegrin domain and a cystein-rich domain. It is interesting that all VAPs have the cystein-rich domain which many snake venom metalloproteinases do not have. In compare with the other snake venom protease without apotosis-inducing activity, there are a lot of specific amino acids for VAPs in metalloproteinase domain. In the disintegrin domain, RGD (Arg-Gly-Asp) sequence is replaced by DECD (Asp Glu-Cys-Asp) or SECD (Ser-Glu-Cys-Asp). The correspondent integrins that bind these motief may play a role in inducing vascular apopt-osis. Further studies into the molecular structure and function of these proteins using site-directed muta-genesis are in progress. These studies may lead to the clarification of a system of vascular degeneration.
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