Cell type-specific activation of intracellular transglutaminase 2 by oxidative stress or ultraviolet irradiation: implications of transglutaminase 2 in age-related cataractogenesis

Transglutaminase (TGase) 2 is a ubiquitously expressed enzyme that modifies proteins by cross-linking or polyamination. An aberrant activity of TGase 2 has implicated its possible roles in a variety of diseases including age-related cataracts. However, the molecular mechanism by which TGase 2 is act...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-04, Vol.279 (15), p.15032
Main Authors: Shin, Dong-Myung, Jeon, Ju-Hong, Kim, Chai-Wan, Cho, Sung-Yup, Kwon, Joon-Cheol, Lee, Hye-Jin, Choi, Kyung-Ho, Park, Sang-Chul, Kim, In-Gyu
Format: Article
Language:English
Subjects:
Aging
Animals
Blotting, Western
Calcium - metabolism
Calcium Chloride - pharmacology
Cataract - enzymology
Cataract - etiology
Cell Line
Cell Line, Tumor
Cells, Cultured
DNA, Complementary - metabolism
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Enzyme Activation
GTP-Binding Proteins - metabolism
Guanosine Triphosphate - pharmacology
HeLa Cells
Humans
Hydrogen Peroxide - pharmacology
K562 Cells
Lens, Crystalline - cytology
Mice
NIH 3T3 Cells
Oxidative Stress
Time Factors
Transfection
Transglutaminases - metabolism
Ultraviolet Rays
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Summary:Transglutaminase (TGase) 2 is a ubiquitously expressed enzyme that modifies proteins by cross-linking or polyamination. An aberrant activity of TGase 2 has implicated its possible roles in a variety of diseases including age-related cataracts. However, the molecular mechanism by which TGase 2 is activated has not been elucidated. In this report, we showed that oxidative stress or UV irradiation elevates in situ TGase 2 activity. Neither the expression level nor the in vitro activity of TGase 2 appeared to correlate with the observed elevation of in situ TGase 2 activity. Screening a number of cell lines revealed that the level of TGase 2 activation depends on the cell type and also the environmental stress, suggesting that unrecognized cellular factor(s) may specifically regulate in situ TGase 2 activity. Concomitantly, we observed that human lens epithelial cells (HLE-B3) exhibited about 3-fold increase in in situ TGase 2 activity in response to the stresses. The activated TGase 2 catalyzed the formation of water-insoluble dimers or polymers of alphaB-crystallin, betaB(2)-crystallin, and vimentin in HLE-B3 cells, providing evidence that TGase 2 may play a role in cataractogenesis. Thus, our findings indicate that in situ TGase 2 activity must be evaluated instead of in vitro activity to study the regulation mechanism and function of TGase 2 in biological and pathological processes.
ISSN:0021-9258
DOI:10.1074/jbc.M308734200