Myotoxic activity of an acidic phospholipase A2 isolated from Lachesis muta (Bushmaster) snake venom.
An acidic phospholipase A2 isolated from Lachesis muta snake venom denoted LM-PLA2, showed neither toxic nor anticoagulant activities in contrast to a potent inhibitory effect of collagen-induced platelet aggregation [Fuly, A.L., Machado. O.L.T., Alves, E.W. and Carlini, C.R., 1997. Thromb. Haemost 78, 1372-1380.]. Now, the myotoxicity induced by LM-PLA2 was investigated by using both in vivo and in vitro experiments. LM-PLA2 induced in vitro a dose- and time-dependent release of creatine-kinase (CK) from mouse Extensor Digitorium Longus (EDL) muscles and also increased the plasma CK activity in treated animals. Histopathological studies confirm myonecrosis of mouse skeletal muscles as a major effect. Edema could also be seen in muscle tissue. The amino-terminal sequence of LM-PLA2 (previously reported) indicates an aspartic acid residue located at position 49, together with other conserved amino acids present in the Asp-49 phospholipases, such as Tyr-28, Gly-30, Gly-32, His-48. Chemical modification of the protein moiety was also performed. Histidine alkylation with p-bromophenacyl bromide and lysine acetylation with acetic anhydride, abolished both indirect hemolytic and myotoxic activities of LM-PLA2. On the other hand, contrarily to what has been observed with several basic myotoxic phospholipases, the myotoxic effect induced by LM-PLA2 was not abolished by heparin.
Fuly
A L
AL
Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janiero, RJ, Brazil.
Calil-Elias
S
S
Zingali
R B
RB
Guimarães
J A
JA
Melo
P A
PA
D000818:Animals; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D009183:Mycotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D010741:Phospholipases A / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D054467:Phospholipases A2; D011817:Rabbits; D014757:Viper Venoms / Q000201:enzymology*; D017819:Viperidae
D009183:Mycotoxins; D014757:Viper Venoms; D003402:Creatine Kinase; D010741:Phospholipases A; D054467:Phospholipases A2