Vely non-specific chelator) [170], polyphenols and flavonoids [173]. Among other things connected for the cellular or extracellular context that may modulate lipoxidation could be the presence of scavengers or quenchers. Although the two terms are usually used interchangeably, scavengers may very well be regarded as non-covalent binders of electrophilic lipids, whereas quenchers would be sturdy nucleophilic compounds reacting with the electrophilic derivatives leading to unmAChR3 Antagonist list reactive solutions. As a result, scavenging or quenching of electrophilic lipids could avert protein lipoxidation. Thus, additionally to endogenous compounds entailing this activity, exogenous all-natural and synthetic quenchers are becoming studied as potential therapeutic tools [170,190]. Certainly one of the best-studied examples will be the dipeptide carnosine composed of -alanine and histidine, which has served because the basis for the synthesis of extra stable analogues, one particular which, generally known as carnosinol, has been located to decrease lipoxidation and showed beneficial effects in animal models of illness [191]. Finally, the presence of other reactive species, either endogenous or exogenous, including drugs and their metabolites can influence lipoxidation by COX-1 Inhibitor drug causing alterations within the cellular antioxidant systems or the protein targets, as well as compete for target residues contributing to PTMs crosstalk. Thus, factors from the cellular context could influence the extent as well as the web-site of protein lipoxidation, contributing to its selectivity and accounting for potential variations in the final results from in vitro and in in vivo studies. 7. Interplay among Post-Translational Modifications Lipoxidation can induce oxidative pressure, as a result eliciting the formation of additional reactive species, responsible for extra PTMs leading to chain reactions with implications in various cellular processes [192]. Furthermore, lipoxidation of enzymes involved in PTMs, such as phosphatases, kinases or deacetylases (see above), can influence PTMs. Therefore, a complicated interplay between PTMs can take spot involving lipoxidation, modifications by other reactive species, and activation or inhibition of proteins catalysing other PTMs. Moreover, direct cooperation or competition among PTMs can occur around the same proteins or residues, which could lead to an increase of protection from lipoxidation, therefore contributing to the generation of very diverse proteoforms and also the complexity of events determining the general outcome. Amongst reactive species potentially competing with electrophilic lipids for modification of proteins are species derived from the oxidation of sugars, ROS and RNS as well as other small molecules, like metabolites of specific amino acids, or even drugs. The modification of cysteine residues can present various examples of this potential competitors, given their capacity to accommodate various modifications [193,194]. In general, it could possibly be regarded as that cysteine oxidation in its numerous forms, such as formation of disulphide bonds, sulfenic and sulfonic acids, nitrosation, and so on., would make the residue significantly less accessible for lipoxidation. Nonetheless, sulfenic acids have already been reported to become more reactive towards certain electrophilic compounds [195], although some disulfides are hugely reactive with oxidants [196]. Thus, in specific cases, cysteine reversible modifications, including disulphide formation, glutathionylation, nitrosation, or addition of NO2 -FAs, could confer protection against far more deleterious ones involving the formati.