Interaction of a snake venom l-amino acid oxidase with different cell types membrane

• Published in: International journal of biological macromolecules 2016-01, Vol.82, p.757-764
• Main Authors: Abdelkafi-Koubaa, Zaineb, Aissa, Imen, Morjen, Maram, Kharrat, Nadia, El Ayeb, Mohamed, Gargouri, Youssef, Srairi-Abid, Najet, Marrakchi, Naziha
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Disk Diffusion Antimicrobial Tests; DNA Damage; Erythrocyte Membrane - drug effects; Erythrocyte Membrane - metabolism; Hemolysis - drug effects; Human health and pathology; Humans; Immobilized enzyme; l-Amino acid oxidase; L-Amino Acid Oxidase - chemistry; L-Amino Acid Oxidase - isolation & purification; L-Amino Acid Oxidase - metabolism; L-Amino Acid Oxidase - toxicity; Life Sciences; Membrane interaction; Phospholipid monolayers; Platelet Aggregation - drug effects; Protein Binding; Rats; Snake Venoms - chemistry
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2015.09.065

Snake venom l-amino acid oxidases are multifunctional enzymes that exhibited a wide range of pharmacological activities. Although it has been established that these activities are primarily caused by the H2O2 generated in the enzymatic reaction, the molecular mechanism, however, has not been fully investigated. In this work, LAAO interaction with cytoplasmic membranes using different cell types and Langmuir interfacial monolayers was evaluated. The Cerastes cerastes venom LAAO (CC-LAAO) did not exhibit cytotoxic activities against erythrocytes and peripheral blood mononuclear cells (PBMC). However, CC-LAAO caused cytotoxicity on several cancer cell lines and induced platelet aggregation in dose-dependent manner. Furthermore, the enzyme showed remarkable effect against Gram-positive and Gram-negative bacteria. These activities were inhibited on the addition of catalase or substrate analogs, suggesting that H2O2 liberation× is required for these effects. Binding studies revealed that CC-LAAO binds to the cell surface and enables the production of highly localized concentration of H2O2 in or near the binding interfaces. On another hand, the interaction of CC-LAAO with a mimetic phospholipid film was evaluated, for the first time, using a monomolecular film technique. Results indicated that phospholipid/CC-LAAO interactions are not involved in their binding to membrane and in their pharmacological activities.