Angiostatin-like molecules are generated by snake venom metalloproteinases.
Angiostatin is a plasminogen-derived anti-angiogenic factor composed of its first four kringle structures. This molecule is generated by proteolytic cleavage of plasminogen by some proteolytic enzymes in vitro. Since venoms of viper snakes are a rich source of both serine- and metalloproteinase, we hypothesized that angiostatin-like polypeptides could be generated during the envenomation after snake bites and play a pathophysiological role in the local tissue damage and regeneration. Our results showed that crude venoms from several species of Bothrops snakes were able to generate angiostatin-like polypeptides and purified metalloproteinases but not serine proteinases from Bothrops jararaca and Bothrops moojeni venoms were responsible for their generation in vitro. The putative plasminogen cleavage sites by the crude venoms and purified proteinases were determined by N-terminal amino acid sequencing of the angiostatin-like molecules. Angiostatin-like peptides derived from human plasminogen digestion by jararhagin, a metalloproteinase isolated from B. jararaca venom, inhibited endothelial cell proliferation in vitro. These results indicate that angiostatin-like molecules can be generated upon snakebite envenomations and may account for the poor and incomplete regenerative response observed in the damaged tissue.
Ho
Paulo Lee
PL
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 05503-900 São Paulo, SP, Brazil. hoplee@usp.br
Serrano
Solange Maria de Toledo
SM
Chudzinski-Tavassi
Ana Marisa
AM
Moura da Silva
Ana Maria
AM
Mentele
Reinhard
R
Caldas
Cristina
C
Oliva
Maria Luiza Vilela
ML
Batista
Isabel Fátima Correia
IF
Oliveira
Maria Leonor Sarno de
ML
D043168:Angiostatins; D000818:Animals; D001483:Base Sequence; D017837:Bothrops; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012910:Snake Venoms / Q000201:enzymology*; D014471:Umbilical Veins / Q000166:cytology
D010446:Peptide Fragments; D010455:Peptides; D012910:Snake Venoms; D043168:Angiostatins; D010958:Plasminogen; D008666:Metalloendopeptidases