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Lecht, Shimon, Chiaverelli, Rachel A, Gerstenhaber, Jonathan, Calvete, Juan J, Lazarovici, Philip, Casewell, Nicholas 
ORCID: https://orcid.org/0000-0002-8035-4719, Harrison, Robert, Lelkes, Peter I and Marcinkiewicz, Cezary
(2015)
'Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki.'. BBA - Biochimica et Biophysica Acta, Vol 1850, Issue 6, pp. 1169-1179.
Abstract
BACKGROUND
Cysteine-rich secretory protein (CRISP) is present in majority of vertebrate including human. The physiological role of this protein is not characterized. We report that a CRISP isolated from Echis carinatus sochureki venom (ES-CRISP) inhibits angiogenesis.
METHODS
The anti-angiogenic activity of purified ES-CRISP from snake venom was investigated in vitro using endothelial cells assays such as proliferation, migration and tube formation in Matrigel, as well as in vivo in quail embryonic CAM system. The modulatory effect of ES-CRISP on the expression of major angiogenesis factors and activation of angiogenesis pathways was tested by qRT-PCR and Western blot.
RESULTS
The amino acid sequence of ES-CRISP was found highly similar to other members of this snake venom protein family, and shares over 50% identity with human CRISP-3. ES-CRISP supported adhesion to endothelial cells, although it was also internalized into the cytoplasm in a granule-like manner. It blocked EC proliferation, migration and tube formation in Matrigel. In the embryonic quail CAM system, ES-CRISP abolished neovascularization process induced by exogenous growth factors (bFGF, vpVEGF) and by developing gliomas. CRISP modulates the expression of several factors at the mRNA level, which were characterized as regulators of angiogenesis and blocked activation of MAPK Erk1/2 induced by VEGF.
CONCLUSIONS
ES-CRISP was characterized as a negative regulator of the angiogenesis, by direct interaction with endothelial cells.
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Cells and Genetics > QU 350 Cellular structures QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/j.bbagen.2015.02.002 |
| Depositing User: | Mary Creegan |
| Date Deposited: | 03 Sep 2015 09:03 |
| Last Modified: | 06 Feb 2018 13:10 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/5284 |
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