Muscle phospholipid hydrolysis by Bothrops asper Asp49 and Lys49 phospholipase A(2) myotoxins - distinct mechanisms of action

作者：Fernandez Julian; Caccin Paola; Koster Grielof; Lomonte Bruno; Gutierrez Jose M; Montecucco Cesare^*; Postle Anthony D

来源：FEBS Journal, 2013, 280(16): 3878-3886.

DOI：10.1111/febs.12386

• fatty acids
• lysophospholipids
• PLA(2) activity
• snake myotoxins
• toxicity

Bothrops snakes are the major cause of ophidian envenomings in Latin America. Mt-I and Mt-II, which share the phospholipase A(2) (PLA(2)) fold, but Mt-II lacks enzymatic activity because the essential active site Asp49 is replaced by Lys. Both myotoxins cause sarcolemma alterations, with Ca2+ entry and loss of A and K+ from muscle cells, but the molecular lesions at the basis of their cellular action are not known, particularly the role of phospholipid hydrolysis. Here we tested their PLA(2) activity invivo, and evaluated the hypothesis that Ca2+-activated endogenous PLA(2)s may be involved in the action of Mt-II. Mt-I and Mt-II in myotubes in culture and in tibialis anterior mouse muscles was determined. Mt-I rapidly hydrolyzed phosphatidylcholine and phosphatidylethanolamine but not phosphatidylserine, but no phospho-lipids were hydrolyzed in the presence of Mt-II. Whole Bothropsasper venom induced a higher extent of phospholipid hydrolysis than Mt-I alone. invivo PLA(2) activity of Mt-I for the first time, and indicate that it acts only on the external monolayer of the sarcolemma. PLA(2)s in the action of Mt-II, implying that plasma membrane disruption by this toxin does not depend on phospholipid hydrolysis. Bothrops myotoxins induce Ca2+ entry and release of A and cause myonecrosis, but through different biochemical mechanisms.

• 出版日期2013-8