Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2.
The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A2 (PLA2) activity. The major component of the venom, a PLA2, here referred to as 'Lemnitoxin', was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A2, are present in Lemnitoxin. This PLA2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2μg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA2.
Laboratory of Neuroimmunoendocrinology and Toxinology, Department of Bioregulation, Institute of Health Sciences (ICS), Federal University of Bahia, Salvador, Bahia, Brazil. Electronic address: luciana.casais@ufba.br.
Luciana L
LL
Casais-E-Silva
Laboratory of Pharmacology, Butantan Institute, São Paulo, Brazil.
Catarina F P
CF
Teixeira
Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, Brazil.
Ivo
I
Lebrun
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Bruno
B
Lomonte
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Alberto
A
Alape-Girón
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
José María
JM
Gutiérrez
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced* / Q000201:enzymology; D004546:Elapid Venoms / Q000201:enzymology* / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D017815:Elapidae / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D018836:Inflammation Mediators / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D054467:Phospholipases A2 / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D017208:Rats, Wistar; D020539:Sequence Analysis, Protein; D013997:Time Factors
D004546:Elapid Venoms; D018836:Inflammation Mediators; C000613948:lemnitoxin protein, Micrurus lemniscatus; C053972:micrurus venom; D003402:Creatine Kinase; D054467:Phospholipases A2
Amino acid sequence; Cytotoxicity; Group I phospholipase A(2); Inflammation; Micrurus lemniscatus; Myotoxicity