The effects of oxidative stress inducing agents on cell signallin

Reversibie phosphorylation of protein tyrosine residues by protein tyrosine kinases (PTK) mediated by polypeptide growth factor receptors (e.g. epidermal growth factor receptor, platelet derived growth factor receptor, insulin receptor) is a signalling process implicated in a variety of processes such as cellular proliferation, differentiation and transformation. On the other hand, many reports converged to the idea that cellular phosphotyrosine levels are regulated by a family of enzymes referred to as protein tyrosine phosphatases (PTP). An essential cysteine residue located in the conserved catalytic domain is responsible for PTP activity. Furthermore, inhibition of PTP activities by oxidative stress inducing agents has been recently documented. It is well known that free radicais and other oxidants at high concentrations are toxic to cells. However, at low concentrations these species may act as modulators/mediators of signal transduction processes in the presence and absence of polypeptide growth factors. Thus, in this article we reviewed our contribution in the general context of the redox modulation of PTK and PTP mediated signal transduction pathways.

Enolizable carbonyl and imino metabolites may act as endogenous sources of reactive oxygen species

Highly reactive oxyradicals and electronically excited triplet carbonyls can be generated in vitro by iron complexes and heme enzyme-catalyzed aerobic oxidation of synthetic or naturally occurring substances capable of enolization in aqueous medium. Monoenols and enamines, obtained by (alpha-methyne-carbonyl and -imine enolization, undergo dioxygen insertion and ultimately originate triplet species; e.g., isobutanal, 3-methylacetoacetone, Schiff bases. In turn, (alpha-hydroxy- and (alpha-aminocarbonyls (e.g., carbohydrates, 5-aminolevulinic acid) tautomerize to enediols and enolamines and yield oxyradicals, initiated by electron transfer to dioxygen, as polyphenols (e.g., 6-hydroxydopamine) and polyphenolamines do. Free radicals and excited species have been implicated in several normal and pathological processes. We here briefly review our contributions to this research area, emphasizing a possible in vivo prooxidant role for 5-aminolevulinic acid, the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acut intermittent porphyria, tyrosinosis).