• The Journal of Korean Medicine
• /
• v.25 no.4
• /
• pp.188-199
• /
• 2004

Transglutaminase 2 (TGase 2) is an enzyme that is widely used in many biological systems for generic tissue stabilization purposes or immediate defenses for wounds. Many reports have showed that TGase 2 is aberrantly activated in tissues and cells and contributes to a variety of diseases, including neurodegenerative diseases and autoimmune diseases. In most cases, the TGase 2 appears to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. However, in other cases such as celiac disease, arthritis, lupus, amyotrophic lateral sclerosis, TGase 2 is involved in the generation of autoantibodies. This suggests the possibility that the inappropriate expression and/or presentation of TGase 2 to T cells might contribute to these diseases in genetically predisposed individuals. Others and we have found that TGase 2 expression is also increased in the inflammation process. We also demonstrated reverse of inflammation by TGase inhibition. Furthermore we discovered the genuine role of TGase 2 in immune cell activation. Increase of TGase activity induces or exacerbates inflammation via NF-κB activation without I-κBα kinase signalings. This review will examine a possibility of TGase inhibitors as therapeutic agents in a variety of inflammatory diseases.

• Tuberculosis and Respiratory Diseases
• /
• v.69 no.5
• /
• pp.337-347
• /
• 2010

Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which $50{\mu}L$ of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/$50{\mu}L$ of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor $(NF)-{\kappa}B$ were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-${\beta}1$ were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-${\alpha}$ and IL-$1{\beta}$ concentrations and $NF-{\kappa}B$ activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-${\beta}1$ concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.

• Microbiology and Biotechnology Letters
• /
• v.24 no.3
• /
• pp.290-298
• /
• 1996

In an effort to understand the role of the conserved domain and of the heterologous one-third part of the carboxy terminal domain of transglutaminase C (TGase II), attempts were made to express TGase II cDNA of human origin in yeast Saccharomyces cerevisiae as in a full-length form as well as in a form of C-terminal truncation. The 2$\mu$-based expression plasmids which contained the TGase II cDNA under the gal inducible promoter were introduced into yeast and the maintenance of the full-length and truncated form of the TGase II gene plasmids were confirmed by Southern blot. The expression of the TGase II gene was analysed by reverse transcription polymerase chain reaction (RT-PCR), and western blot analyses. As assayed by [1,4$^{14}$C]-putrescine incorporation into succinylated casein, the full-lenth as well as the truncated forms of recombinant TGase II showed some catalytic activity. These results indicate that the N-terminal homologous domain of human TGase II retains a catalytically active domain. The level of TGase II expressed in yeast, however, was far lower than satisfactory and other expression system should be sought further chracterization of the enzyme. The negative effect of TGase II on the growth of yeast is interesting with respect to the physiological effect of TGase II in cornification of epidermal keratinocytes.

• Food Science of Animal Resources
• /
• v.34 no.6
• /
• pp.808-814
• /
• 2014

This study investigated the effect of gum arabic (GA) combined with microbial transglutaminase (TG) on the functional properties of porcine myofibrillar protein (MP). As an indicator of functional property, heat-set gel and emulsion characteristics of MP treated with GA and/or TG were explored under varying NaCl concentrations (0.1-0.6 M). The GA improved thermal gelling ability of MP during thermal processing and after cooling, and concomitantly added TG assisted the formation of viscoelastic MP gel formation. Meanwhile, the addition of GA decreased cooking yield of MP gel at 0.6 M NaCl concentration, and the yield was further decreased by TG addition, mainly attributed by enhancement of protein-protein interactions. Emulsion characteristics indicated that GA had emulsifying ability and the addition of GA increased the emulsification activity index (EAI) of MP-stabilized emulsion. However, GA showed a negative effect on emulsion stability, particularly great drop in the emulsion stability index (ESI) was found in GA treatment at 0.6 M NaCl. Consequently, the results indicated that GA had a potential advantage to form a viscoelastic MP gel. For the practical aspect, the application of GA in meat processing had to be limited to the purposes of texture enhancer such as restructured products, but not low-salt products and emulsion-type meat products.

• International Journal of Oral Biology
• /
• v.42 no.4
• /
• pp.191-196
• /
• 2017

Transglutaminase2 (TGM2) is a multi-functional calcium dependent enzyme that affects angiogenesis, apoptosis, differentiation, attachment, and changes in the extracellular matrix. However, its function in periodontal tissue has not yet been studied. The aim of this study was to investigate the association of the TGM2 expression and the modulation of inflammatory mediators in inflamed periodontal ligament (PDL) cells induced by pro-inflammatory cytokines such as Interleukin-$1{\beta}$ and the Tumor necrosis $factor-{\alpha}$. The expression of TGM2 was increased in the inflamed periodontal tissue and PDL cells. Over-expressed TGM2 in the PDL cells increased expression of MMP1, MMP3, IL-6, CXCL8, and PTGS2. Conversely, inhibition of TGM2 activity using LDN27219, a TGM2 inhibitor, resulted in decreased expression of MMP1, MMP3, IL-6, and CXCL8. The mRNA expression was confirmed by RT-PCR and quantified by qRT-PCR. Protein levels were also confirmed by immunofluoroscence staining. These results suggest that TGM2 plays an important role in the regulation of inflammatory mediators which exacerbate tissue damage in inflamed periodontal tissue.

• BMB Reports
• /
• v.34 no.1
• /
• pp.66-72
• /
• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.11
• /
• pp.3893-3898
• /
• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

• Food Science of Animal Resources
• /
• v.29 no.4
• /
• pp.415-422
• /
• 2009

In this study, several factors were analyzed in an effort to determine the effects of transglutaminase (TGase) treatment on sodium caseinate (NaCN), ${\alpha}--lactalbumin$ (${\alpha}-La$), and ${\beta}-lactoglobulin$ (${\beta}-Lg$) polymerization reactions. The results of SDSPAGE showed that NaCN was slightly hydrolyzed to molecular weights of 50-400 kDa according to activation time. ${\alpha}-La$ formed high-molecular polymers of 30-300 kDa, whereas ${\beta}-Lg$ remained almost completely unhydrolyzed. Melting temperatures of NaCN, ${\alpha}-La$ with and without TGase were all in the range of $100{\pm}10^{\circ}C$ under the endothermic curve, and the melting temperature of ${\beta}-Lg$ with TGase was lower than that with TGase. When the proteins were incubated for 3 h with TGase, the micrographic structures showed a small quantity of sediment and broad layers. The final ${\alpha}-La$ residues remained at a level of 21.38%, and the TGase-treated ${\alpha}-La$ was confirmed to have undergone a profound loss of mass, to 18.25%. The DPPH-radical scavenging activity of NaCN and ${\beta}-Lg$ with TGase treatment was higher than that observed in the untreated sample, while those of ${\alpha}-La$ increased with concentration.

• Asian-Australasian Journal of Animal Sciences
• /
• v.19 no.1
• /
• pp.137-143
• /
• 2006

The purpose of this study was to prepare a binder containing porcine blood transglutaminase (TGase), thrombin and fibrinogen. Extracted TGase, thrombin and fibrinogen were used alone or mixed with different proportions of their volume (v/v/v) by nine combinations as follows were 0.5:1:15, 0.5:1:20, 0.5:1:25, 1:1:15, 1:1:20, 1:1:25, 1.5:1:15, 1.5:1:20 and 1.5:1:25, respectively. Five ml of each combination were mixed with 0.6 ml of 0.25 M calcium chloride before experiment. After storage at 4C for 0, 1, 2, 3, 4 and 5 weeks, enzyme activity, total plate count, pH value, and SDS-PAGE of TGase, thrombin and fibrinogen were tested and pH value, clotting time and gel strength of the nine combination binders were determined. The results showed that total plate count of thrombin and pH value of TGase were significantly higher (p<0.05) than in other treatments. SDS-PAGE results showed that purified TGase, thrombin and fibrinogen from porcine blood plasma compared with commercial products (Sigma) had the same band patterns and nine different combination binders had no significant effect. Enzymatic activity of TGase and thrombin decreased as storage time increased. Total plate count of TGase, thrombin and fibrinogen and clotting time of the binder increased as storage time increased. The higher amount of fibrinogen in combinations, the stronger the gel strength.

• Korean Journal of Food Science and Technology
• /
• v.30 no.5
• /
• pp.1152-1157
• /
• 1998

In this study, an attempt was made to obtain the optimum setting condition of frozen mackerel surimi prepared from alkaline washing under atmospheric, 660 and 560 mmHg pressure. Mackerel surimi were incubated at 15, 25, 35 and $45^{\circ}C$ for 2, 4, 6, 8 and 10 hr, respectively, followed by heating at $90^{\circ}C$ for 25 min to be cooked gel. The qualities of surimi gels were examined by analyzing the transglutaminase (TGase) activity, gel strength and scanning electron microscopy (SEM). For the preparation of mackerel surimi gel, optimum condition of setting was incubation at $35^{\circ}C$ for 6 hr.