期刊
JOURNAL OF PROTEOMICS
卷 103, 期 -, 页码 137-152出版社
ELSEVIER
DOI: 10.1016/j.jprot.2014.03.034
关键词
Snake venom; Elapidae; Hydrophiinae Sea snake; Pelamis platura
资金
- Ministerio de Economia y Competitividad, Madrid [BFU2010-17373]
- Generalitat Valenciana, Spain [PROMETEO/2010/005]
- Network for proteomic characterization of snake venoms of medical and biological relevance in Latin America [741-B3-760]
- CYTED [P211RT0412]
- Ministry of Environment of Costa Rica, resolutions [SINAC-ACG-012-201, SINAC-ACAT 069-2012]
The yellow-bellied sea snake, Pelarnis platura, is the most broadly distributed snake species. Despite being endowed with a highly lethal venom, a proteomic analysis of its toxin composition was unavailable. The venoms of specimens collected in Golfo de Papagayo and Golfo Dulce (Costa Rica), where two distinctive color morphs occur, were chromatographically compared. The latter inhabits a fjord-like gulf where the transit of oceanic sea snakes into and from the basin is restricted, thus possibly affecting gene flow. RP-HPLC evidenced a conserved venom protein profile in both populations, despite their divergent color phenotypes. Following a trend observed in other sea snakes, P. platura venom is relatively simple, being composed of proteins of the three-finger toxin (3FTx), phospholipase A(2) (PLA(2)), cysteine-rich secretory protein (CRISP), 5'-nucleotidase, and metalloproteinase families. The first three groups represent 49.9%, 32.9%, and 9.1% of total venom protein, respectively. The most abundant component (-26%) is pelamitoxin (P62388), a short-chain 3FTx, followed by a major basic PLA(2) (-20%) and a group of three isoforms of CRISPs (similar to 9%). Whereas isolated pelamitoxin was highly lethal to mice, neither the PLA(2) nor the CRISP fraction caused death. However, the PLA(2) rapidly increased plasma creatine kinase activity after intramuscular injection, indicating its myotoxic action. Differing from myotoxic PLA(2)s of viperids, this PLA2 was not cytolytic to murine myogenic cells in vitro, suggesting possible differences in its mechanism of action. The median lethal dose (LD50) estimates for P. platura crude venom in mice and in three species of fishes did not differ significantly. The sea snake antivenom manufactured by CSL Ltd. (Australia), which uses Enhydrina schistosa as immunogen, cross-recognized the three major components of P. platura venom and, accordingly, neutralized the lethal activity of crude venom and pelamitoxin, therefore being of potential usefulness in the treatment of envenomations by this species. Biological significance Integrative analyses of animal venoms that combine the power of proteomics (venomics) with the characterization of their functional and immunological properties are significantly expanding knowledge on these remarkable bioweapons, both from a basic and a medical perspective. Costa Rica harbors a unique population of the yellow-bellied sea snake, Pelamis platura, that is restricted to a fjord-like gulf (Golfo Dulce). This population differs markedly from oceanic populations found elsewhere along the Pacific coast of this country, by presenting a patternless bright yellow coloration, instead of the typical bicolored or tricolored pattern of this species. It has been suggested that the dominance of this yellow-morph in Golfo Dulce might reflect gene flow restrictions, caused by the oceanographic conditions at this location. The present study demonstrates that the remarkable phenotypic variation between the two color morphs inhabiting Golfo Dulce and Golfo de Papagayo, respectively, is not associated with differences in the expression of venom components, as shown by their conserved RP-HPLC profiles. Proteomic analysis revealed the relatively simple toxin composition of P. platura venom, which contains three predominant types of proteins: three-finger toxins (protein abundance: 49.9%), phospholipases A (32.9%), and cysteine-rich secretory proteins (9.1%), together with few minor componepts. Further, the involvement of these most abundant proteins in the toxic effects of the venom, and their cross-recognition and neutralization by a sea snake antivenom produced against the venom of Enhydrina schistosa, were analyzed. (C) 2014 Elsevier B.V. All rights reserved.
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