Oxidativestress is a result of imbalance between the generation of reactive oxygenspecies (ROS) and the antioxidant defense systems, leading to cellular damage.It has been found to be associated with the initiation and progression of avariety of human diseases. In many typesof cells, oxidativestress has been shown to drive the S-glutathionylation of free thiol groups(-SH) on the cysteine residues of proteins to form protein-glutathione mixeddisulfide adducts (Pr-SSG). ProteinS-glutathionylation is a dynamic reversible process and regulates the structureand function of target proteins. De-glutathionylation is mainly catalyzed byglutaredoxin (Grx), a thiol disulfide oxido-reductase (thioltransferase).
Inrecent years, the research team led by associate Prof. ZHANG Xue /Prof. KEYuehai from Zhejiang University School of Medicine has conducted systematicresearch into protein post-translational modification. The latest researchresults were published in the journal Nature Communications on December 07, andentitled “Oxidative stress-induced FABP5 S-glutathionylation protects againstacute lung injury by suppressing inflammation in macrophages”.
Oxidativestress contributes to the pathogenesis of acute lung injury. ProteinS-glutathionylation plays an important role in cellular antioxidant defense. Researchersreport that the expression of deglutathionylation enzyme Grx1 is decreased inthe lungs of acute lung injury mice. The acute lung injury induced by hyperoxiaor LPS is significantly relieved in Grx1 KO and Grx1fl/flLysMcre mice, confirming the protective role of Grx1-regulated S-glutathionylation inmacrophages. Using a quantitative redox proteomics approach, researchers show thatFABP5 is susceptible to S-glutathionylation under oxidative conditions.S-glutathionylation of Cys127 in FABP5 promotes its fatty acid binding abilityand nuclear translocation. Further results indicate S-glutathionylationpromotes the interaction of FABP5 and PPARβ/δ, activates PPARβ/δ target genesand suppresses the LPS-induced inflammation in macrophages. Our study reveals amolecular mechanism through which FABP5 S-glutathionylation regulatesmacrophage inflammation in the pathogenesis of acute lung injury.
