Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch

Abstract

H 2 O 2 permeation through a cell membrane significantly affects living organisms, and permeation is controlled by the physico-chemical nature of lipids and other membrane components. We investigated the molecular relationship between H 2 O 2 permeation and lipid membrane structure using three oxidized lipids. POVPC and PazePC act as intra- and inter-molecular permeation promoters, respectively; however, their underlying mechanisms were different. The former changed the partition equilibrium, while the latter changed the permeation pathway. PoxnoPC inhibited permeation under our experimental conditions via an intra-molecular configuration change. Thus, both intra- and inter-molecular processes were found to control the role of oxidized lipids as inhibitors and promoters towards H 2 O 2 permeation with different mechanisms depending on structure and composition. Here, we identified two independent H 2 O 2 permeation routes: (i) permeation through lipid membrane with increased partition coefficient by intra-molecular configurational change and (ii) diffusion through pores (water channels) formed by inter-molecular configurational change of oxidized lipids. We provide new insight into how biological cells control permeation of molecules through intra- and inter-molecular configurational changes in the lipid membrane. Thus, by employing a rational design for both oxidized lipids and other components, the permeation behaviour of H 2 O 2 and other ions and molecules through a lipid membrane could be controlled.

Reactive oxygen species rescue regeneration after silencing the MAPK–ERK signaling pathway in Schmidtea mediterranea

“…S7 ). Also, H 2 O 2 is able to cross cell membranes on its own or via hydrophobic pores induced by configuration changes of oxidized lipids initiated via intra- and intermolecular processes 19 , 55 – 57 .…”

Self-Regulated and Bidirectional Communication in Synthetic Cell Communities

“…Moreover, if the sender GUVs did not have α-HL but still the light triggered adhesions and/or if external H 2 O 2 was added, there was no increase in receiver permeability (Figure a,b). These findings exclude increased membrane tension and lipid oxidation as alternative mechanisms that could increase the membrane permeability and show that α-HL is essential for the contact-dependent increase in permeability. Additional proof for contact-dependent permeabilization was provided by experiments in which sulfo-Cy5 was added externally to the aforementioned GUVs, and a sulfo-Cy5 signal inside receiver GUVs that were in contact with sender GUVs was bleached (Figure S10 and Movie 2).…”

Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: Rising Threat to Antimicrobial Therapy

“…This helps bacteria survive in harmful environments. 49 It is necessary to collect evidence for the different strategies of the pathogen that reduce the permeability or change the pore size of OMPs. The general diffusion porins OmpF, OmpC, PhoE OmpA, OmpD, and OmpX actively contribute to reducing the permeability in Salmonella for hydrophilic antibiotics.…”

“…Without restrictions, hydrogen peroxide (H 2 O 2 ) is capable of passing through membranes, but because the OMPs possess reduced permeability, H 2 O 2 cannot pass through them. This helps bacteria survive in harmful environments . It is necessary to collect evidence for the different strategies of the pathogen that reduce the permeability or change the pore size of OMPs.…”