ABSTRACT
Oxidative stress in cellular environments may cause lipid oxidation and membrane degradation. Therefore, studying the degree of lipid membrane morphological changes by reactive oxygen and nitrogen species will be informative in oxidative stress-based therapies. This study introduces the possibility of using scanning electrochemical microscopy as a powerful imaging technique to follow the topographical changes of a solid-supported lipid bilayer model induced by reactive species produced from gas plasma. The introduced strategy is not limited to investigating the effect of reactive species on the lipid bilayer but could be extended to understand the morphological changes of the lipid bilayer due to the action of membrane proteins or antimicrobial peptides.
Subject(s)
Lipid Bilayers , Microscopy, Electrochemical, ScanningABSTRACT
Several studies have revealed that various diseases such as cancer have been associated with elevated phospholipase A2 (PLA2 ) activity. Therefore, the regulation of PLA2 catalytic activity is undoubtedly vital. In this study, effective inactivation of PLA2 due to reactive species produced from cold physical plasma as a source to model oxidative stress is reported. We found singlet oxygen to be the most relevant active agent in PLA2 inhibition. A more detailed analysis of the plasma-treated PLA2 identified tryptophan 128 as a hot spot, rich in double oxidation. The significant dioxidation of this interfacial tryptophan resulted in an N-formylkynurenine product via the oxidative opening of the tryptophan indole ring. Molecular dynamics simulation indicated that the efficient interactions between the tryptophan residue and phospholipids are eliminated following tryptophan dioxidation. As interfacial tryptophan residues are predominantly involved in the attaching of membrane enzymes to the bilayers, tryptophan dioxidation and indole ring opening leads to the loss of essential interactions for enzyme binding and, consequently, enzyme inactivation.
