Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

Abstract

CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions.

• Authors: Yi-Ling Chiou, Ying-Jung Chen, Shinne-Ren Lin, Long-Sen Chang
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 58 Issue 6-7 Pg. 518-26 (Nov 2011) ISSN: 1879-3150 [Electronic] England
• PMID: 21906610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Elapid Venoms
• Membrane Lipids
• Phospholipids
• Phospholipases A2
• Calcium

Topics

• Calcium (metabolism)
• Cell Line, Tumor
• Cell Membrane Permeability (drug effects)
• Elapid Venoms (toxicity)
• Female
• Humans
• Membrane Fusion (drug effects)
• Membrane Lipids (metabolism)
• Phospholipases A2 (physiology)
• Phospholipids (metabolism)