Transglutaminase 2 induces nitric oxide synthesis in BV-2 microglia

Park, Key Chung; Chung, Kyung Cheon; Kim, Yoon-Seong; Lee, Jongmin; Joh, Tong H.; Kim, Soo-Youl

doi:10.1016/j.bbrc.2004.08.204

Cited by 34 publications

(35 citation statements)

References 34 publications

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“…These results suggest that TG activity might augment the pathway of NF-κB activation in a self-enhancing manner to induce iNOS expression and NO production after LPS triggering. It is consistent with some reports in microglial cell line, BV-2, in which TG activity is increased by LPS exposure and inhibitors of TG activity reduce LPS-induced NO production (Park et al, 2004;Lee et al, 2004). The authors of these reports proposed that TG2 could activate NF-κB via a novel pathway; rather than stimulating phosphorylation and degradation of the inhibitory subunit α of NF-κB (I-κBα), but the polymerization of I-κBα by TG activity to regulate iNOS transcription .…”

Section: Discussionsupporting

confidence: 93%

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

Takano

Shiraiwa

Moriyama

et al. 2010

Neurochemistry International

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Abstract-Activation of glia has been observed in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis and brain ischemia. Excessive production of nitric oxide (NO), as a consequence of increased inducible NO synthase (iNOS) in glia, contributes to neurodegeneration. Transglutaminase 2 (TG2) is a cross-linking enzyme, which is activated in neurodegenerative diseases such as PD, AD and Huntington's diseases. However, mechanisms contributing to the increased TG activity in neurodegenerative diseases remain to be clarified. In the present study, we examined the expression of TG2 in cultured rat hippocampal astrocytes activated with lipopolysaccharide (LPS), which is generally used for a stimulant of iNOS induction. The expressions of TG2 mRNA and protein were increased by stimulation with LPS in a dose-dependent manner. The LPS-induced TG2 expression was diminished by ammonium pyrrolidine-1-carbodithioate; an inhibitor for nuclear factor (NF)-κB activation, suggesting the factors involved. Both expressions of TG2 and iNOS induced by LPS stimulation were suppressed by an antioxidant, ethyl pyruvate, in a dose-dependent manner. Furthermore, they were also suppressed by cystamine, an inhibitor of TG activity. These results suggest that the level of TG2 expression is regulated by oxidative stress and the activity of TG itself, and that the induction of iNOS and NO production are closely associated with TG2 expression in LPS-stimulated activation of astrocytes.

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Section: Discussionsupporting

confidence: 93%

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

Takano

Shiraiwa

Moriyama

et al. 2010

Neurochemistry International

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“…[27][28][29] In the cytoplasm, TG2 can catalyze polymer formation of I-B␣ monomers, thereby it contributes to the activation of nuclear factor-B in microglia and breast cancer cells. 30,31 To ascertain whether TG2 may be implicated in ATRA-induced gene expression regulation in NB4 cells, total gene expression profiling was carried out.…”

Section: Discussionmentioning

confidence: 99%

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Csomós

Német

Fésüs

et al. 2010

Blood

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“…20). As far as septic shock is concerned, TG2 expression has been reported to be induced by LPS in several tissues and organs (21)(22)(23). Use of in vitro cell lines has shown that an increase in TG2 activity is associated with NF-B activation (24).…”

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confidence: 99%

Transglutaminase Type II Is Involved in the Pathogenesis of Endotoxic Shock

Falasca

Farrace

Rinaldi

et al. 2008

The Journal of Immunology

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The pathogenesis of sepsis is characterized by the inability of the host to regulate the inflammatory response, and as a consequence, dysregulated inflammatory processes induce organ dysfunctions and death. Altered transglutaminase type II (TG2) expression is associated with the development of many inflammatory diseases. Therefore, in this study, we questioned whether TG2 could also contribute to the pathological inflammatory dysregulation occurring in septic shock in vivo. To this aim, we used as an experimental model the TG2 knockout mice, in which the process of septic shock was elicited by treatment with LPS. Interestingly, our results demonstrated that TG2 ablation leads to partial resistance to experimental sepsis. The increased survival of TG2−/− mice was reflected in a drastic reduction of organ injury, highlighted by a limited infiltration of neutrophils in kidney and peritoneum and by a better homeostasis of the proinflammatory mediators as well as mitochondrial function. We also showed that in wild-type mice, the TG2 expression is increased during endotoxemia and, being directly involved in the mechanisms of NF-κB activation, it may cause a continuous activation cycle in the inflammatory process, thus contributing to development of sepsis pathogenesis. We propose that the inhibition of TG2 could represent a novel approach in the treatment of inflammatory processes associated with sepsis.

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Transglutaminase 2 induces nitric oxide synthesis in BV-2 microglia

Cited by 34 publications

References 34 publications

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

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

Tissue transglutaminase contributes to the all-trans-retinoic acid–induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia

Transglutaminase Type II Is Involved in the Pathogenesis of Endotoxic Shock

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