title: Monitoring of transglutaminase 2 under different oxidative stress conditions.
abstract: Transglutaminase 2 (TG2) is a multifunctional calcium-dependent enzyme which catalyzes the post-translational protein crosslinking with formation of intra- or inter-molecular epsilon(gamma-glutamyl)lysine bonds or polyamine incorporation. The up-regulation and activation of TG2 have been reported in a variety of physiological events, including cell differentiation, signal transduction, apoptosis, and wound healing, as well as in cell response to stress evoked by different internal and external stimuli. Here we review TG2 role in cell response to redox state imbalance both under physiological and pathological conditions, such as neurodegenerative disorders, inflammation, autoimmune diseases and cataractogenesis, in which oxidative stress plays a pathogenetic role and also accelerates disease progression. The increase in TG activity together with mitochondrial impairment and collapse of antioxidant enzymatic cell defences have been reported to be the prominent biochemical alterations becoming evident prior to neurodegeneration. Moreover, oxidative stress-induced TG2 pathway is involved in autophagy inhibition and aggresome formation, and TG2 has been suggested to function as a link between oxidative stress and inflammation by driving the decision as to whether a protein should undergo SUMO-mediated regulation or proteasomal degradation. Literature data suggest a strong association between oxidative stress and TG2 up-regulation, which in turn may result in cell survival or apoptosis, depending on cell type, kind of stressor, duration of insult, as well as TG2 intracellular localization and activity state. In particular, it may be suggested that TG2 plays a pro-survival role when the alteration of cell redox state homeostasis is not associated with intracellular calcium increase triggering TG2 transamidation activity.
authors.affiliation: Dip. Scienze Biochimiche, Fisiologiche e della Nutrizione, Policlinico Universitario, University of Messina, Via Consolare Valeria, 98125, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccamo
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Condello
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins