Transglutaminase inhibitor cystamine alleviates the abnormality in liver from NZB/W F1 mice

Hsu, Tsai‐Ching; Huang, Chih Yang; Chiang, Szu Yi; Lai, Wen Xian; Tsai, Chang Hai; Tzang, Bor‐Show

doi:10.1016/j.ejphar.2007.10.059

Cited by 25 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…129 Therefore, amine substrates, such as putrescine and cystamine (competitive inhibitors of the crosslinking activity of the enzyme), have been shown to be protective in ethanol-induced liver injury as well as liver fibrosis induced by CCl 4 . 138, 139, 140 …”

Section: Fibrogenic Versus No or Anti-fibrogenic Functions Of Tg2mentioning

confidence: 99%

Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Furutani²,

et al. 2016

View full text Add to dashboard Cite

Transglutaminase 2 (TG2) is primarily known as the most ubiquitously expressed member of the transglutaminase family with Ca2+-dependent protein crosslinking activity; however, this enzyme exhibits multiple additional functions through GTPase, cell adhesion, protein disulfide isomerase, kinase, and scaffold activities and is associated with cell growth, differentiation, and apoptosis. TG2 is found in the extracellular matrix, plasma membrane, cytosol, mitochondria, recycling endosomes, and nucleus, and its subcellular localization is an important determinant of its function. Depending upon the cell type and stimuli, TG2 changes its subcellular localization and biological activities, playing both anti- and pro-apoptotic roles. Increasing evidence indicates that the GTP-bound form of the enzyme (in its closed form) protects cells from apoptosis but that the transamidation activity of TG2 (in its open form) participates in both facilitating and inhibiting apoptosis. A difficulty in the study and understanding of this enigmatic protein is that opposing effects have been reported regarding its roles in the same physiological and/or pathological systems. These include neuroprotective or neurodegenerative effects, hepatic cell growth-promoting or hepatic cell death-inducing effects, exacerbating or having no effect on liver fibrosis, and anti- and pro-apoptotic effects on cancer cells. The reasons for these discrepancies have been ascribed to TG2's multifunctional activities, genetic variants, conformational changes induced by the immediate environment, and differences in the genetic background of the mice used in each of the experiments. In this article, we first report that TG2 has opposing roles like the protagonist in the novel Dr. Jekyll and Mr. Hyde, followed by a summary of the controversies reported, and finally discuss the possible reasons for these discrepancies.

show abstract

Section: Fibrogenic Versus No or Anti-fibrogenic Functions Of Tg2mentioning

confidence: 99%

Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Furutani²,

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In many tissues, enhanced TG2 activity, which results from cell damage due to chronic inflammation, is required for TGF-β activation via crosslinking of large latent complexes to the cell surface, or to fibronectin and other ECM components through the latent TGF-β binding protein portion. Amine donor substrates, such as putrescine and cystamine, which act as competitive inhibitors for TG2 in its crosslinking reaction, have been shown to protect against CCl4-induced fibrosis [40]. Thus, chronic expression of TG2 may promote cell survival and permit accumulation of oncogenic mutations, resulting in cell transformation and tumor progression (Figure 1).…”

Section: Tg2 and Inflammationmentioning

confidence: 99%

Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

Mehta

Han

2011

Cancers

View full text Add to dashboard Cite

Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

show abstract

“…GPT2 is implicated in exacerbating autoimmune disease [86], and its levels were shown to be increased in NZB/NZW F1 mice [87]. Increased serum aminotransferases have been reported to be associated with anti-mitochondrial antibodies in SLE patients with autoimmune liver disease [88].…”

Section: Cellular Molecular and Functional Basis For Gene Selectmentioning

confidence: 99%

Genes, tolerance and systemic autoimmunity

Singh

Waldron

Hahn

2012

Autoimmunity Reviews

View full text Add to dashboard Cite

The characterization of functional CD8+ inhibitory or regulatory T cells and their gene regulation remains a critical challenge in the field of tolerance and autoimmunity. Investigating the genes induced in regulatory cells and the regulatory networks and pathways that underlie mechanisms of immune resistance and prevent apoptosis in the CD8+ T cell compartment are crucial to understanding tolerance mechanisms in systemic autoimmunity. Little is currently known about the genetic control that governs the ability of CD8+ Ti or regulatory cells to suppress anti-DNA Ab production in B cells. Silencing genes with siRNA or shRNA and overexpression of genes with lentiviral cDNA transduction are established approaches to identifying and understanding the function of candidate genes in tolerance and immunity. Elucidation of interactions between genes and proteins, and their synergistic effects in establishing cell-cell cross talk, including receptor modulation/antagonism, are essential for delineating the roles of these cells. In this review, we will examine recent reports which describe the modulation of cells from lupus prone mice or lupus patients to confer anti-inflammatory and protective gene expression and novel associated phenotypes. We will highlight recent findings on the role of selected genes induced by peptide tolerance in CD8+ Ti.

show abstract

Transglutaminase inhibitor cystamine alleviates the abnormality in liver from NZB/W F1 mice

Cited by 25 publications

References 37 publications

Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

Genes, tolerance and systemic autoimmunity

Contact Info

Product

Resources

About