Structural and biological characterization of a crotapotin isoform isolated from Crotalus durissus cascavella venom

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• 作者：de Oliveira ; Daniela G. ; Toyama ; Marcos H. ; Martins ; Alice M.C. ; Havt ; Alexandre ; Nobre ; Arlâ ; ndia C.L. ; et. al.
• 关键词：Crotalus durissus cascavella ; Crotapotin isoform ; PLA₂ ; Venom ; Rattlesnake ; Neurotoxins
• 刊名：Toxicon
• 出版年：2003
• 出版时间：July, 2003
• 年：2003
• 卷：42
• 期：1
• 页码：53-62
• 全文大小：486 K

文摘

Envenoming by Crotalus durissus subspecies leads to coagulation disorders, myotoxicity, neurotoxicity and acute renal failure. The most serious systemic alteration and primary cause of death after snakebite is acute renal failure. In this work, we isolated crotapotin, an acid component (Crtp) of crotoxin from Crotalus durissus cascavella venom and we investigated its bactericidal and pro-inflammatory activities as well as its renal effects in rat isolated perfused kidneys. Crtp was bactericidal to the Gram-negative species Xanthomonas axonopodis pv. passiflorae, but was less effective against the Gram-positive Claribacteri ssp, probably because of differences in the cell wall composition. Crtp showed a high amino acid sequence homology with other Crtps described in the literature (around of 90 % ) and its A and B chains had high conserved regions corresponding to the calcium-binding loop, catalytic site and helix 3 of PLA₂. The Crtp showed moderate pro-inflammatory activity and increased significantly the inflammation evoked by PLA₂ when co-injected or co-incubated with PLA₂. The renal parameters evaluated included the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR) and percent of sodium tubular transport ( % TNa⁺). Crotapotin (5 μg/ml) significantly increased the PP and RVR, whereas the GFR, UF and % TNa⁺ were unaffected. These results suggest that crotoxin is the main venom component responsible for nephrotoxicity and crotapotin contributes little to this phenomenom. The biological and bactericidal actions of Crtp also suggest that this protein may have functions other than simply acting as a chaperone for PLA₂.