scholarly journals Tissue Transglutaminase, Not Lysyl Oxidase, Dominates Early Calcium-Dependent Remodeling of Fibroblast-Populated Collagen Lattices

2014 ◽  
Vol 200 (2) ◽  
pp. 104-117 ◽  
Author(s):  
D.D. Simon ◽  
L.E. Niklason ◽  
J.D. Humphrey
Keyword(s):  
Lysyl Oxidase ◽  
Tissue Transglutaminase ◽  
Calcium Dependent ◽  
Collagen Lattices

Expression Of Tissue Transglutaminase Is Associated With Glucocorticoid Resistance In T-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3853-3853
Author(s):  
Hyun Joo Jung ◽  
Seong Wook Lee ◽  
Jun Eun Park
Keyword(s):  
T Cell ◽  
Abc Transporters ◽  
Conflicts Of Interest ◽  
Tissue Transglutaminase ◽  
Lymphoblastic Leukemia ◽  
Glucocorticoid Resistance ◽  
Calcium Dependent ◽  
Cycle Arrest ◽  
Dependent Protein ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Glucocorticoids are core drugs in the treatment of T-cell acute lymphoblastic leukemias (T-ALL) because they induce apoptosis and cell-cycle arrest in leukemia lymphoblasts. The treatment response to glucocorticoid is the most important predictive factor for treatment outcome of T-ALL. Development of secondary glucocorticoid resistance is lethal to the patients at relapse. To improve survival for glucocorticoid-resistant T-ALL patients, it is necessary to develop new therapeutic strategies to overcome glucocorticoid resistance. In the present study, we used biochemical and molecular methodologies to demonstrate that tissue transglutaminase (TG2) confers glucocorticoid resistance in T-ALL. TG2 is a calcium-dependent protein crosslinking enzyme reported to be overexpressed in various metastatic or chemotherapy-resistant cancer cells including lymphoma cells. We found that T-ALL cells expressed elevated levels of TG2. We generated a model of glucocorticoid-adapted subclones of T-ALL cell lines that were extremely less sensitive to glucocorticoid than the parent cells. Glucocorticoid-adapted subclones not only showed the change of ABC transporters activity but also increased TG2 expression and activity than the parent cells in T-ALL. Inhibition of TG2 suppressed glucocorticoid resistance and improved the cytotoxicity of glucocorticoid in glucocorticoid-adapted subclones of T-ALL. Our study is the first to show the expression of TG2 and the contribution of TG2 to glucocorticoid resistance in T-ALL. The modulation of TG2 expression could be a new therapeutic target to overcome glucocorticoid resistance in T-ALL. Furthermore, change of TG2 expression could serve as markers of secondary glucocorticoid resistance in T-ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Glucocorticoid-induced cell-derived matrix modulates transforming growth factor β2 signaling in human trabecular meshwork cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Felix Yemanyi ◽  
Janice Vranka ◽  
Vijay Krishna Raghunathan
Keyword(s):  
Growth Factor ◽  
Trabecular Meshwork ◽  
Transforming Growth Factor ◽  
Lysyl Oxidase ◽  
Tissue Transglutaminase ◽  
Smooth Muscle Actin ◽  
Plasminogen Activator Inhibitor ◽  
Transglutaminase 2 ◽  
Tissue Growth ◽  
Type I

Abstract Aberrant remodeling of trabecular meshwork (TM) extracellular matrix (ECM) may induce ocular hypertensive phenotypes in human TM (hTM) cells to cause ocular hypertension, via a yet unknown mechanism. Here, we show that, in the absence of exogenous transforming growth factor-beta2 (TGFβ2), compared with control matrices (VehMs), glucocorticoid-induced cell-derived matrices (GIMs) trigger non-Smad TGFβ2 signaling in hTM cells, correlated with overexpression/activity of structural ECM genes (fibronectin, collagen IV, collagen VI, myocilin), matricellular genes (connective tissue growth factor [CTGF], secreted protein, acidic and rich in cysteine), crosslinking genes/enzymes (lysyl oxidase, lysyl oxidase-like 2–4, tissue transglutaminase-2), and ECM turnover genes/enzymes (matrix metalloproteinases-MMP2,14 and their inhibitors-TIMP2). However, in the presence of exogenous TGFβ2, VehMs and GIMs activate Smad and non-Smad TGFβ2 signaling in hTM cells, associated with overexpression of α-smooth muscle actin (α-SMA), and differential upregulation of aforementioned ECM genes/proteins with new ones emerging (collagen-I, thrombospondin-I, plasminogen activator inhibitor, MMP1, 9, ADAMTS4, TIMP1); with GIM-TGFβ2-induced changes being mostly more pronounced. This suggests dual glaucomatous insults potentiate profibrotic signaling/phenotypes. Lastly, we demonstrate type I TGFβ receptor kinase inhibition abrogates VehM-/GIM- and/or TGFβ2-induced upregulation of α-SMA and CTGF. Collectively, pathological TM microenvironments are sufficient to elicit adverse cellular responses that may be ameliorated by targeting TGFβ2 pathway.

scholarly journals Calcium blockers decrease the bortezomib resistance in mantle cell lymphoma via manipulation of tissue transglutaminase activities

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2568-2578 ◽  
Author(s):  
Hyun Joo Jung ◽  
Zheng Chen ◽  
Michael Wang ◽  
Luis Fayad ◽  
Jorge Romaguera ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Tissue Transglutaminase ◽  
Therapeutic Strategies ◽  
Calcium Blockers ◽  
Downstream Signaling ◽  
Calcium Dependent ◽  
Mantle Cell ◽  
Signaling Axis ◽  
Dependent Protein

Abstract Although bortezomib is clinically approved for the treatment of mantle cell lymphoma (MCL), only limited effects of this treatment have been demonstrated. To improve survival for bortezomib-resistant patients, it is necessary to develop new therapeutic strategies. In the present study, we used biochemical and molecular methodologies to demonstrate that tissue transglutaminase (TG) activates downstream NF-κB signaling pathways. The signaling axis from TG to NF-κB could be a new therapeutic target to overcome bortezomib resistance in MCL. TG2 is a calcium-dependent protein cross-linking enzyme reported to be overexpressed in various cancer cells. We found that MCL cells expressed elevated levels of TG2 and that the modification of TG2 activities altered NF-κB expression and downstream signaling in MCL cells. When TG2 signaling was inhibited by calcium blockers, the combination of a calcium blocker (perillyl alcohol) with bortezomib suppressed NF-κB expression and improved the cytotoxicity of bortezomib in MCL cells. Our study is the first to show the expression of TG2 and the contribution of TG2 to NF-κB signaling in MCL. TG2 inhibition may be used as an alternative target anti-MCL therapy, and calcium blockers may be combined with bortezomib to overcome the bortezomib resistance in MCL.

Genomic analysis of C-type lectins

2002 ◽  
Vol 69 ◽  
pp. 59-72 ◽  
Author(s):  
Kurt Drickamer ◽  
Andrew J. Fadden
Keyword(s):  
Biological Effects ◽  
Cell Signalling ◽  
Genomic Analysis ◽  
Binding Activity ◽  
Immunoglobulin Superfamily ◽  
Carbohydrate Binding ◽  
Carbohydrate Recognition ◽  
Calcium Dependent ◽  
Binding Domains ◽  
Carbohydrate Recognition Domains

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell–cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

Tissue transglutaminase, the celiac disease autoantigen, preferentially generates antigenic neoepitopes in γ and γ but not in α gliadins

2001 ◽  
Vol 120 (5) ◽  
pp. A684-A684
Author(s):  
D TRAPP ◽  
W DIETERICH ◽  
H WIESER ◽  
M LEIDENBERGER ◽  
D SEILMEIER ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase

HLA-DQ2 and/or-DQ9 is associated with coeliac disease specific autoantibodies to tissue transglutaminase in families with thyrold autoimmunity

2001 ◽  
Vol 120 (5) ◽  
pp. A393-A393
Author(s):  
D SCHUPPAN ◽  
W DIETERICH ◽  
S HOFMANN ◽  
M HUEFNER ◽  
K USADEL ◽  
...  
Keyword(s):  
Coeliac Disease ◽  
Tissue Transglutaminase ◽  
Disease Specific ◽  
Hla Dq2

Antifungal alkaloids from Agelas Citrina that decouple calcium-dependent excitation-contraction

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
TF Molinski ◽  
EP Stout ◽  
LCY Yu ◽  
KM Truong ◽  
IN Pessah
Keyword(s):  
Calcium Dependent

Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
I Schlottmann ◽  
M Ehrhart-Bornstein ◽  
M Wabitsch ◽  
SR Bornstein ◽  
V Lamounier-Zepter
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Human Adipocytes ◽  
Fatty Acid Binding ◽  
Calcium Dependent ◽  
Acid Binding Protein
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