Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Abstract

The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10–50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening.

Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease

“…A combination of membrane phospholipid degradation and FA accumulation could disrupt membrane structure and fluidity and alter cell-cell signaling [30,31]. Insertion of free FA into membranes could also create membrane pores [32], a phenomenon that can facilitate pathogen destruction in concert with antimicrobial peptides and amyloid proteins [3]. Hydrophobic A␤ may act as an antimicrobial peptide in the brain to combat microbes that gain access to CSF due to increased permeability caused by BBB disruption [33].…”