2011 Fiscal Year Final Research Report
Exploring evolutional origins of viper venom haemorrhagic factors
| Project/Area Number |
23657146
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Developmental biology
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| Research Institution | Kyoto University |
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Principal Investigator |
SEHARA Atsuko 京都大学, 再生医科学研究所, 教授 (60209038)
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| Project Period (FY) |
2011
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| Keywords | 器官形成 |
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| Research Abstract |
Snake venoms are classified mainly into two categories : neurotoxic and hemorrhagic venoms. This study addressed questions on the latter venom, what are the evolutional origins of viper hemorrhagic venom proteins or how vipers acquired them during evolution. Viper haemorrhagic factors are produced as precursor soluble factors composed of two toxic polypeptide domains, a domain of haemorrhagic activity and that of anti-coagulation activity. The precursors are similar in structure to transmembrane proteins generically named as ADAMs(a disintegrin and metalloproteases). We hypothesized that viper venoms mimicked ADAMs of ancestral vertebrates that carried functions in vasculogenesis/angiogenesis and/or behaviors of blood cells. We previously showed that ADAM8 is involved in the onset of blood circulation in zebrafish embryos by live imaging of their blood vessels and erythroblasts(Iida et al., Curr Biol., 2010.). By using this imaging technique, we examined how viper venom haemorrhagic venoms affects vasculogenesis or integrity of blood vessels, As a result, we found that some of them inhibited vasculogenesis of zebrafish embryos. Then we examine whether ADAM8 ply some roles on blood vessel formation. Injection of antisense morpholino oligonucleotides against ADAM8 into eggs caused inhibitory effects on elongation of intersegmental vessels. Live imaging and electron micrographs of those embryos revealed that blood cells attached to blood vessels abnormally and gene expression in blood vessels was significantly altered in those embryos. Haemorrhagic activities of viper venom proteins could be related to regulatory roles of ADAM8 in vasculogenesis.
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[Journal Article] ADAM12 produces by tumor cells rather than stromal cells accelerates breast tumor progression2011
Author(s)
Frohlich, C., Nehammar, C., Albrechtsen, R., Kribqvist, P., Kveiborg, M., Sehara-Fujisawa, A., Mercurio, AM. Wewer, UM.
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Journal Title
Mol. Cancer Res.
Volume: 9
Pages: 1449-61
DOI
Peer Reviewed
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[Journal Article] Generation of a monoclonal antibody reactive to prefusion myocytes.2011
Author(s)
Kurisaki, T., Masuda, A., Nakagiri, S., Hayata, Y., Kuhara, M., Kishi, Y., Sehara-Fujisawa, A.
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Journal Title
J. Muscle Res. Cell Motil.
Volume: 32
Pages: 31-38
Peer Reviewed
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