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Tissue transglutaminase and the stress response

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Summary.

The expression of the protein crosslinking enzyme tissue transglutaminase (TG2, tTG), the ubiquitous member of transglutaminase family, can be regulated by multiple factors. Although it has been suggested that TG2 can be involved in apoptotic cell death, high levels of enzyme have also been associated with cell survival in response to different stimuli. Furthermore, evidence indicates that increases in TG2 production cause enzyme translocation to cell membrane. Cell stress can also lead to TG2 accumulation on the cell surface and in the extracellular matrix resulting in changes in cell-matrix interactions.

Here, we discuss the underlying mechanisms of TG2 up-regulation induced by various stimuli including glutamate exposure, calcium influx, oxidative stress, UV, and inflammatory cytokines.

These findings agree with a postulated role for transglutaminases in molecular mechanisms involved in several diseases suggesting that cross-linking reactions could be a relevant part of the biochemical changes observed in pathological conditions.

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Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid

CD:

celiac disease

ECM:

extracellular matrix

FN:

fibronectin

GYKI 52466:

1-(4′-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzo-diazepine

IFN-γ:

interferon-γ

LPA:

lysophosphatidic acid

TGF-beta:

transforming growth factor-beta

MK-801:

(+)-5-Methyl-10,11-dihydro-5H-dibenzo [a, d]-cyclohepten-5,10-imine hydrogen maleate

NF-κB:

nuclear factor-kappa B

NMDA:

N-methyl-D-aspartic acid

3-NP:

3-nitropropionic acid

PLA2:

phospholipase A2

ROS:

reactive oxygen species

TG(s):

transglutaminase(s)

TG2:

tissue transglutaminase

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Authors and Affiliations

  1. Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy

    R. Ientile & D. Caccamo

  2. School of Life and Health Sciences, Aston University, Birmingham, U.K.

    M. Griffin

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  1. R. Ientile
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  2. D. Caccamo
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  3. M. Griffin
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Ientile, R., Caccamo, D. & Griffin, M. Tissue transglutaminase and the stress response. Amino Acids 33, 385–394 (2007). https://doi.org/10.1007/s00726-007-0517-0

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