title: 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: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors: Yi-Ling
authors: YL
authors: Chiou
authors: Ying-Jung
authors: YJ
authors: Chen
authors: Shinne-Ren
authors: SR
authors: Lin
authors: Long-Sen
authors: LS
authors: Chang
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D004546:Elapid Venoms / Q000633:toxicity*; D005260:Female; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism*; D054467:Phospholipases A2 / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D004546:Elapid Venoms; D008563:Membrane Lipids; D010743:Phospholipids; D054467:Phospholipases A2; D002118:Calcium