Transglutaminase 2 expression induced by lipopolysaccharide stimulation together with NO synthase induction in cultured astrocytes

Takano, Katsura; Shiraiwa, Kazumi; Moriyama, Mitsuaki; Nakamura, Yoichi

doi:10.1016/j.neuint.2010.08.019

Cited by 22 publications

(22 citation statements)

References 54 publications

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“…In the current study, we have shown that inhibition of TGM2 activity by cystamine decreased the calcification and ALP activity in VSMC from CKD rats. It should be pointed out that in addition to inhibition of TGM2 activity, cystamine is also potent inducer of antioxidants such as glutathione and L -cysteine in vivo and in vitro [16,17]. Furthermore, oxidative stress is known to be a risk factor for vascular calcification in CKD [18].…”

Section: Discussionmentioning

confidence: 99%

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

et al. 2013

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Background: Transglutaminase 2 (TGM2) is a calcium-dependent enzyme that can cross-link nearly all extracellular matrix (ECM) proteins and can facilitate cell-ECM interaction through integrins. Given the importance of the ECM in vascular calcification we tested the hypothesis that increased TGM2 activity may accelerate vascular calcification in chronic kidney disease (CKD). Methods: We utilized thoracic aortas and vascular smooth muscle cells (VSMC) from the Cy/+ rat, a model of progressive CKD that develops arterial calcification on a normal phosphorus diet, compared to normal rats. Results: VSMC isolated from CKD rats had increased expression and activity of TGM2 compared to cells from normal rats. The increased calcification and expression of alkaline phosphatase activity observed in VSMC from CKD rats compared to normal was inhibited in a dose-dependent manner with the TGM inhibitors cystamine and Z006. Matrix vesicles (MV) from CKD rat VSMC also had increased TGM2 expression and the calcification of MV on type I collagen could be inhibited with cystamine and accelerated by exogenous cross-linking of fibronectin or type I collagen with TGM2. Finally, the calcification of aorta rings from CKD rats in ex vivo cultures was inhibited with TGM2 inhibitor. Conclusion: These data demonstrate a role of TGM2 in the pathogenesis of vascular calcification in CKD through enhancement of MV-ECM calcification.

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Section: Discussionmentioning

confidence: 99%

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

et al. 2013

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“…79, 80 TG2 expression is induced by oxidative stress, and the induction of inducible NO synthase and NO production, which contribute to neurodegeneration, are closely associated with TG2 expression in the lipopolysaccharide-stimulated activation of astrocytes. 81 The infarction volume was smaller in both TG2 knockout mice and mice treated with cystamine than in control mice. 82 In contrast, both SH-SY5Y human neuroblastoma cells 83 and a permanent middle cerebral artery ligation stroke model 84 demonstrated that hypoxic conditions increased nuclear TG2, TG2 binding to HIF1 β independently of transamidase activity, and the prevention of the upregulation of pro-apoptotic Bnip3 85 and Noxa, 86 thereby protecting neuronal cells from hypoxia-induced death in ischemia and stroke.…”

Section: Neuroprotective Versus Neurodegenerative Roles By Modulatingmentioning

confidence: 90%

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

Furutani²,

et al. 2016

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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.

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“…Amounts of NO 2 - accumulated in the medium were determined by a fluorometric method using 2,3-diaminonaphthalene (DAN) (Dojindo, Kumamoto, Japan), as described previously [13]. BV-2 cells (4 × 10 4 cells/well) replated onto 96-well plates were stimulated with 300 ng/ml LPS for 24 h. A 100-µl aliquot of cell-free supernatant was mixed with 20 µl of DAN solution; DAN stock solution (5 mg/ml in 0.62 M HCl) was freshly diluted 100 times with 0.62 M HCl.…”

Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide-Stimulated Transglutaminase 2 Expression Enhances Endocytosis Activity in the Mouse Microglial Cell Line BV-2

Kawabe

Takano

Moriyama

et al. 2014

Neuroimmunomodulation

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Objectives: In peripheral macrophages, tissue-type transglutaminase (TG2) is reported to be involved in phagocytosis of apoptotic cells. However, the contribution of TG2 to microglial phagocytosis has not been investigated. In this study, using a microglial cell line, BV-2, we examined the changes in TG2 expression, phagocytosis and pinocytosis in cells stimulated by lipopolysaccharide (LPS). Methods: Cells of the mouse microglial cell line BV-2 were stimulated by LPS with or without cystamine, an inhibitor of TG enzyme activity, for 24 h. TG2 expression was measured by real-time RT-PCR and Western blotting. TG activity was evaluated using biotinylated pentylamine as a substrate. Pinocytosis was determined by uptake of 1-µm fluorescent microbeads. Phagocytosis was assessed by uptake of dead cells, human neuroblastoma SH-SY5Y cells, which were pretreated with H₂O₂ for 24 h. Results: Phagocytosis of dead cells and pinocytosis of fluorescent microbeads were up-regulated by LPS stimulation together with TG2 expression. Blockade of TG enzyme activity by cystamine suppressed TG2 expression, phagocytosis and pinocytosis. Conclusions: These results suggested that LPS-induced TG2 was involved in the mechanism of pinocytosis and phagocytosis in microglia.

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Transglutaminase 2 expression induced by lipopolysaccharide stimulation together with NO synthase induction in cultured astrocytes

Cited by 22 publications

References 54 publications

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

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

Lipopolysaccharide-Stimulated Transglutaminase 2 Expression Enhances Endocytosis Activity in the Mouse Microglial Cell Line BV-2

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