Redox Signaling by Reactive Electrophiles and Oxidants

Abstract

The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation, (2) physicochemical properties, (3) mechanisms of action, (4) methods of interrogation, and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.

Review—Quantification of Hydrogen Peroxide by Electrochemical Methods and Electron Spin Resonance Spectroscopy

“…Together with reactive nitrogen species (RNS), calcium ions and others, these are universal signaling species in cells. [2][3][4][5][6][7][8][9][10][11][12] In principle, H 2 O 2 is formed by a sequential 2e¯transfer to O 2 , whereby the intermediate radical • O 2¯i s produced. • O 2¯i s subsequently protonated resulting in the nonradical H 2 O 2 .…”

Stable, Wavelength‐Tunable Fluorescent Dyes in the NIR‐II Region for In Vivo High‐Contrast Bioimaging and Multiplexed Biosensing

“…No apparent spectral change for CX dyes (10 mm)in phosphate-buffered saline (PBS) was observed upon addition of glutathione,cysteine, hydrogen sulfide,hydrogen peroxide, peroxynitrite,orhypochlorite (OCl À )uptotheir corresponding physiological concentration [14] (Supporting Information, Figures S12-30). No apparent spectral change for CX dyes (10 mm)in phosphate-buffered saline (PBS) was observed upon addition of glutathione,cysteine, hydrogen sulfide,hydrogen peroxide, peroxynitrite,orhypochlorite (OCl À )uptotheir corresponding physiological concentration [14] (Supporting Information, Figures S12-30).…”

Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1

“…Conversely, HNE-stimulation of HuR-knockdown cells elicited a general downregulation of global transcriptional activity compared to control cells ( Figure 1A and S3). Given the important roles that pleiotropic covalent drugs and native RES play on Nrf2 signaling (Hayes and Dinkova-Kostova, 2014;Parvez et al, 2018), we homed in on differentially-expressed Nrf2-driven genes. This analysis revealed an interesting bifurcation between HuR-dependent effects on Nrf2-driven genes in nonstimulated shHuR cells versus HNE-stimulated cells.…”

“…The central player in AR is Nrf2, a transcription factor that controls the expression of numerous genes for cytoprotection and detoxification (Hayes and Dinkova-Kostova, 2014). AR is intrinsically linked to reactive electrophilic and oxidative species (RES/ROS), which are increasingly appreciated as bona fide cell signaling cues (Parvez et al, 2018). Upon stimulation with either endogenous or environmental RES/ROS, the cell mounts a stress defense through Nrf2/AR upregulation.…”