Glutamate‐evoked redox state alterations are involved in tissue transglutaminase upregulation in primary astrocyte cultures

Abstract

The aim of this study was to evaluate the involvement of oxidative stress in glutamate-evoked transglutaminase (TGase) upregulation in astrocyte cultures (14 DIV). A 24 h exposure to glutamate caused a dose-dependent depletion of glutathione intracellular content and increased the ROS production in cell cultures. These effects were receptor-mediated, as demonstrated by inhibition with GYKI 52466. The pre-incubation with glutathione ethyl ester or cysteamine recovered oxidative status and was effective in significantly reducing glutamate-increased tissue TGase. These data suggest that tissue TGase upregulation may be part of a biochemical response to oxidative stress induced by a prolonged exposure of astrocyte cultures to glutamate.

Transglutaminase 2 expression induced by lipopolysaccharide stimulation together with NO synthase induction in cultured astrocytes

“…An NF-κB inhibitor, APDC, decreased the LPS-stimulated induction of TG2, suggesting that NF-κB might be associated with that induction. The fact that the NF-κB binding site is identified on the TG2 promoter region (Caccamo et al, 2005a(Caccamo et al, , 2005bCampici et al, 2003Campici et al, , 2004 gives further support to the involvement of NF-κB signaling pathways in mechanisms underlying the up-regulation of TG2 mRNA and protein by LPS stimulation in cultured astrocytes.…”

“…Moreover, these reports also suggest the involvement of ROS in glial activation; glutamate induces TG2 up-regulation, through redox state alteration or increase of intracellular ROS followed by NF-κB activation (Caccamo et al, 2005a(Caccamo et al, , 2005bCampici et al, 2003Campici et al, , 2004. Lee et al (2003) indicated that lysophosphatidic acid and transforming growth factor-β induced the increase of intracellular ROS followed by activation of TG2, which was blocked by ROS scavengers, N-acetyl-L-cysteine and catalase.…”

Transglutaminase is a Therapeutic Target for Oxidative Stress, Excitotoxicity and Stroke: A new Epigenetic Kid on the Cns Block

“…42 Jun and Fos, members of the AP-1 family, have been shown to induce TG2 transcription in neurons or glia 41 and this upregulation usually correlates with cell death. Building on prior work that showed that TG2 could be induced by a host of extracellular factors in glial cells, 43,44 we have recently showed that lethal, glutathione depletion-induced oxidative stress induces TG2 upregulation in cortical neurons 36 and that inhibition of TG in neurons prevents oxidative death. By contrast, protective concentrations of peroxide generated in astrocytes leads to downregulation of TG2 message.…”

Expression of Tissue Transglutaminase in Human Thyroid Cancer Cell Lines: Effect of Novel Enantiopure Triazole Derivatives

“…In preliminary experiments, a lot of the both cell cultures were exposed to different concentrations of synthesized triazole derivatives (-)5b and (-)6d [53] (0.5, 1, 5, 10, 25, 50, 100 µM) for 12, 24, 48 hr, in order to establish the optimal concentrations and their exposure times to the triazole derivates [28,62,63]. For this purpose, MTT test and morphological characterization were utilized [30].…”

“…In contrast, when TG2 is localized into the nuclear compartment, it phosphorylates different proteins, including retinoblastoma protein (Rb), a substrate for TG2 kinase activity [19]. Aberrant TG2 expression contributes to a variety of disease processes [20], including cancer [21][22][23][24][25], neurodegenerative diseases [26][27][28][29][30][31], autoimmune diseases, such as celiac disease [32,33], rheumatoid arthritis [34,35], tissue fibrosis [36].…”