Disease relevance of Tgm1

• The role of transglutaminase in the rat subtotal nephrectomy model of renal fibrosis [1].
• We investigated the therapeutic potential of sodium butyrate and factor XIII and the role of transglutaminase during mucosal repair in experimental colitis [2].
• BACKGROUND/AIMS: Butyrate and factor XIII may improve ulcerative colitis; they also affect tissue and serum transglutaminase levels [2].
• Finally, we propose a model for ischemia/reperfusion injury in which the extent of proteolytic and transglutaminase activities ultimately determines whether apoptosis or necrosis is achieved [3].
• Differential transglutaminase distribution in normal rat liver and rat hepatoma [4].

Psychiatry related information on Tgm1

• We recently found that alternative transcripts of tissue transglutaminase (tTG or TG2) were present in hippocampal brain regions of Alzheimer's disease (AD), but not in control, non-demented, age-matched brains [5].

High impact information on Tgm1

• Transglutaminase is essential in receptor-mediated endocytosis of alpha 2-macroglobulin and polypeptide hormones [6].
• Recovery of visual response of injured adult rat optic nerves treated with transglutaminase [7].
• The transglutaminase activity of rat liver TGase II expressed in COS-1 cells was inhibited by the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) or by alpha 1-adrenergic receptor activation [8].
• Regeneration of central nervous system axons in fish is correlated with the presence of a transglutaminase [7].
• Application of this nerve-derived transglutaminase to rat optic nerves, in which the injury had caused the loss of visual evoked potential response to light, promoted the recovery of that response within 6 weeks after injury [7].

Chemical compound and disease context of Tgm1

• This observed association between tissue transglutaminase, epsilon-(gamma-glutamyl) lysine cross-link, and renal tubulointerstitial scarring in rats submitted to SNx suggests that tissue transglutaminase may play an important role in the development of experimental renal fibrosis and the associated loss of tubule integrity [1].
• BACKGROUND & AIMS: Butyrate is effective in experimental colitis by increasing transglutaminase activity [9].
• Butyrate, mesalamine, and factor XIII in experimental colitis in the rat: effects on transglutaminase activity [2].
• Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma [4].
• Transglutaminase catalyzes the formation of covalent bonds between protein glutamine residues and primary amines and has been found recently to be potently activated by tetanus toxin, a dichain clostridial protein that selectively blocks neurotransmitter secretion [10].

Biological context of Tgm1

• The number of cells showing increases in tissue transglutaminase and its cross-link product, epsilon-(gamma-glutamyl) lysine appeared greater than those showing signs of typical apoptosis as determined by in situ end-labeling [1].
• Increased nuclear conjugated polyamines and transglutaminase during liver regeneration [11].
• It also suggests that a specific induction of the cytosolic tissue transglutaminase may be involved in the TGF-beta 1-induced pathways of apoptotic cell death in McA-RH7777 hepatoma cells [12].
• Expression and localization of TG are not well established during wound healing [13].
• This activated Ca(2+)-dependent tissue transglutaminase, forming a cross-linked protein scaffold, and also opened the mitochondrial permeability transition pore, causing outer mitochondrial membrane rupture, increased cytosolic cytochrome c, activation of procaspase 3, internucleosomal DNA fragmentation, and ultrastructural features of apoptosis [14].

Anatomical context of Tgm1

• Two transglutaminase-mediated modifications of the rat epididymal spermatozoon surface were demonstrated in vitro [15].
• Gastric mucosa was examined histologically and grossly, and transglutaminase activity was measured as the Ca(2+)-dependent covalent incorporation of [3H]putrescine into acid-precipitable protein [16].
• A covalent dimer of interleukin (IL)-2, produced in vitro by the action of a nerve-derived transglutaminase, has been shown previously to be cytotoxic to mature rat brain oligodendrocytes [17].
• Induction of apoptosis by transforming growth factor-beta 1 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression [12].
• We demonstrate that the plasma, macrophages and nerves of fish contain a 55 kDa form of transglutaminase that cross-reacts immunologically with the a-subunit of FXIII in mammals (80 kDa) [18].

Associations of Tgm1 with chemical compounds

• Similarly, transglutaminase activity and epsilon-(gamma-glutamyl) lysine were also predominately located within glomeruli and were much more intense in the PAN-injected group than that in control animals [19].
• Transglutaminase was effective in promoting the binding of spermidine to the sperm [15].
• Tissue homogenates showed no significant change in overall transglutaminase activity (14C putrescine incorporation assay) unless adjusted for the loss of viable tubule cells, when an increase from 5.77+/-0.35 to 13.93+/-4.21 U/mg DNA in cytosolic tissue transglutaminase activity was seen [1].
• Transglutaminase, reduced in the colons of the saline group (783 +/- 157 vs. normal 1800 +/- 192 mU/g; P < 0.01), returned toward normal values in the sodium butyrate or sodium butyrate plus mesalamine groups (1390 +/- 228 and 1226 +/- 172 mU/g, respectively; P < 0.01 vs. saline) [2].
• Electrophilic metabolites may stimulate apoptosis by decreasing thiols, increasing [Ca2+], and activating Ca(2+)-dependent transglutaminase and endonucleases [20].

Physical interactions of Tgm1

• Alpha 1B-adrenoceptor interacts with multiple sites of transglutaminase II: characteristics of the interaction in binding and activation [21].
• Tissue transglutaminase (TG) is an enzyme that stabilizes the structure of tissues by covalently ligating extracellular matrix molecules [13].
• Calcium pretreatment induces the decrease in epidermal growth factor binding through the activation of transglutaminase in isolated liver membrane [22].
• We demonstrated the invagination of transferrin into reticulocyte plasma membrane to learn whether membrane-bound transglutaminase (TGase, a Ca(2+)-dependent enzyme) is involved in this invagination [23].

Regulatory relationships of Tgm1

• Hepatocyte growth factor induces transglutaminase activity that negatively regulates the growth signal in primary cultured hepatocytes [24].
• Recently, it has been shown that the calreticulin (CRT) down-regulates both GTP binding and transglutaminase activities of TGII [25].
• The receptor-mediated endocytosis of alpha 2-macroglobulin can be inhibited by a diverse group of chemical compounds all of which share the property of being inhibitors of one form of cellular transglutaminase [6].
• Covalent modification of synapsin I by a tetanus toxin-activated transglutaminase [10].
• A moderate increase of transglutaminase activity in neonatal primary mouse keratinocytes was induced by both factors at concentrations of about 300 pg TGF beta/ml and 10 pg chalone fraction/ml [26].

Other interactions of Tgm1

• Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats [19].
• Transglutaminase ( TGase ) activity was not affected in any significant manner by PRL or CyA in most tissues studied [27].
• A 13-residue structure with the consensus sequence GSQLKSFGQVKSS is repeated 13 times within the SVS II protein and appears to be involved in the formation of the rat copulatory plug via a transglutaminase reaction cross-linking glutamine and lysine residues [28].
• Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 117 nM hepatocyte growth factor (HGF) [24].
• We previously reported that a novel GTP binding protein (G alpha h) is tissue type transglutaminase (TGII) and transmits the alpha 1B-adrenoceptor (AR) signal to phospholipase C (PLC) through its GTPase function [21].

Analytical, diagnostic and therapeutic context of Tgm1

• This increase was supported by Western blot analysis, showing a parallel increase in renal tissue transglutaminase content [1].
• Immunohistochemistry demonstrated that this large increase in epsilon-(gamma-glutamyl) lysine cross-link and tissue transglutaminase took place predominantly in the cytoplasm of tubular cells, while immunofluorescence also showed low levels of the epsilon-(gamma-glutamyl) lysine cross-link in the extracellular renal interstitial space [1].
• The lung transglutaminase was found to be distinct from tissue transglutaminase (identifiable with the well-characterized guinea pig liver transglutaminase) in its retention volume in DEAE-Sephacel columns and its Kd value in gel-filtration columns [29].
• Immunohistochemistry on cryostat sections revealed a sixfold increase (P < 0.001) in ECM-bound tTg antigen at 90-d post-SNx, whereas in situ transglutaminase activity demonstrated by the incorporation of fluorescein cadaverine into cryostat sections indicated a 750% increase (P < 0.001) on day 90 in SNx animals [30].
• Within the first hour after axotomy TG activity is rapidly and transiently elevated [31].

References