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PMID:10728833
Citation |
Fuly, AL, Calil-Elias, S, Zingali, RB, Guimarães, JA and Melo, PA (2000) Myotoxic activity of an acidic phospholipase A2 isolated from Lachesis muta (Bushmaster) snake venom. Toxicon 38:961-72 |
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Abstract |
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. |
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Keywords |
Animals; Creatine Kinase/blood; Creatine Kinase/metabolism; Mice; Muscles/drug effects; Muscles/pathology; Mycotoxins/chemistry; Mycotoxins/isolation & purification; Mycotoxins/toxicity; Phospholipases A/chemistry; Phospholipases A/isolation & purification; Phospholipases A/toxicity; Phospholipases A2; Rabbits; Viper Venoms/enzymology; Viperidae |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
enables |
GO:0004623: phospholipase A2 activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
GO:0004623: phospholipase A2 activity |
ECO:0000314: |
F |
Figure 3 |
complete | ||||
See also
References
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