先端生物医学研究とイノベーション

Membrane Lipid Oxidation as a Negative Feedback Loop Modulating Cell Response to Oxidative Stress

Chekashkina KV, Bashkirov PV and Pavlov KV*

Reactive oxygen species (ROS) are implicated in originating multiple deleterious processes, including inflammation of the airways, heart diseases, carcinogenesis, age-related neurodegenerative conditions, etc. Less commonly discussed are the beneficial and/or inevitable effects associated with their normal production in healthy cells and tissues. Lipid oxidation by ROS can be viewed as playing a dual role, including upregulation of certain proteins required for the protection of cells and tissues against abnormally high ROS concentrations, thereby constituting a negative feedback loop required for dynamic stability of homeostasis. Analysis of recent publications and the original experimental results provide convincing, if circumstantial, evidence in support of this hypothesis. Gradual decrease of membrane rigidity (bending modulus) accompanied by the change of other mechanical parameters was observed in a model system based on lipid membrane nanotubes (LNT) pulled out of planar lipid bilayers. The experimental system was optimized for real-time measurements of membrane mechanical parameters. The obtained results offer credible explanation to the seemingly paradoxical behavior of certain membrane proteins, such as intracellular divalent cation transporters, ryanodine receptors, or endosomal ion channels in response to oxidative stress; they also suggest novel treatment strategies involving combined use of rare lipid species and photosensitizers, e.g., in order to minimize collateral damage inflicted by phototherapy.