title: Cell type-specific activation of intracellular transglutaminase 2 by oxidative stress or ultraviolet irradiation: implications of transglutaminase 2 in age-related cataractogenesis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Dong-Myung
authors.initials: DM
authors.lastname: Shin
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Chai-Wan
authors.initials: CW
authors.lastname: Kim
authors.forename: Sung-Yup
authors.initials: SY
authors.lastname: Cho
authors.forename: Joon-Cheol
authors.initials: JC
authors.lastname: Kwon
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Choi
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Park
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
mesh_terms: D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002386:Cataract / Q000201:enzymology* / Q000209:etiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020014:K562 Cells; D007908:Lens, Crystalline / Q000166:cytology; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013997:Time Factors; D014162:Transfection; D011503:Transglutaminases / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D018076:DNA, Complementary; D006160:Guanosine Triphosphate; D006861:Hydrogen Peroxide; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002122:Calcium Chloride; D002118:Calcium