Nitric Oxide and Electrophilic Cyclopentenone Prostaglandins in Redox signaling, Regulation of Cytoskeleton Dynamics and Intercellular Communication

Abstract

Nitric oxide (NO) and electrophilic cyclopentenone prostaglandins (CyPG) are local mediators that modulate cellular response to oxidative stress in different pathophysiological processes. In particular, there is increasing evidence about their functional role during inflammation and immune responses. Although the mechanistic details about their relationship and functional interactions are still far from resolved, NO and CyPG share the ability to promote redox-based post-translational modification (PTM) of proteins that play key roles in cellular homeostasis, signal transduction and transcription. NO-induced S-nitrosylation and S-glutathionylation as well as cyclopentenone-mediated adduct formation, are a few of the main PTMs by which intra- and inter-cellular signaling are regulated. There is a growing body of evidence indicating that actin and actin-binding proteins are susceptible to covalent PTM by these agents. It is well known that the actin cytoskeleton is key for the establishment of interactions among leukocytes, endothelial and muscle cells, enabling cellular activation and migration. In this review we analyze the current knowledge about the actions exerted by NO and CyPG electrophilic lipids on the regulation of actin dynamics and cytoskeleton organization, and discuss some open questions regarding their functional relevance in the regulation of intercellular communication.

Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles

“…In particular, glutathionylation of proteins is catalyzed by glutathione S-transferases and can protect or mitigate protein oxidation. Protein S-glutathionylation is also a tool to modulate protein function and cellular processes including apoptosis, calcium homeostasis [ 101 ], glycolysis [ 102 ] and cytoskeleton dynamism [ 103 ]. For example, glutathionylation of p53 can induce accumulation of damaged mitochondria and apoptosis [ 104 ].…”

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“…Piperlongumine has also been shown to interfere with T-cell differentiation and is considered to be a selective immunosuppressant 67 , partly, again by a pro-oxidative action, here due to intracellular depletion of glutathione levels 74 . This was linked to the inhibition of the transcription factors RORC (RORγt), HIF1A and STAT3, resulting in reduced production of IL22, IL17A, IL17F, and subsequent inhibition of Th17-differentiation, but not of regulatory Th1 and Th2 cells (Tregs), along with reduced expression of CD69 and CD35 expression markers 67,74,76 .…”

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