Inhibition of tissue transglutaminase attenuates lipopolysaccharide-induced inflammation in glial cells through AKT/mTOR signal pathway

Ding, Yirong; Zhang, Ji; Wang, Rui

doi:10.1016/j.biopha.2017.03.027

Cited by 5 publications

(6 citation statements)

References 49 publications

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“…It has been suggested that mTOR play crucial roles in the development of acute lung injury, because pharmacological inhibition or genetic deletion of mTOR resulted in attenuated airway inflammation and lung injury ( 35 – 37 ). Interestingly, several studies have found that inflammatory stimuli activated mTOR both in vitro and in vivo ( 36 , 38 – 40 ). Some studies suggested that LPS-induced activation of PI3K–AKT pathway might be responsible for the activation of mTOR ( 40 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, several studies have found that inflammatory stimuli activated mTOR both in vitro and in vivo ( 36 , 38 – 40 ). Some studies suggested that LPS-induced activation of PI3K–AKT pathway might be responsible for the activation of mTOR ( 40 , 41 ). However, this study found that the activation of mTOR might also result from the impaired suppression of mTOR by the dephosphorylation of AMPK in LPS-exposed mice.…”

Section: Discussionmentioning

confidence: 99%

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Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

Fan

et al. 2018

Front. Immunol.

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AMP-activated protein kinase (AMPK) is a crucial metabolic regulator with profound modulatory activities on inflammation. Although the anti-inflammatory benefits of AMPK activators were well documented in experimental studies, the pathological significance of endogenous AMPK in inflammatory disorders largely remains unknown. This study investigated the phosphorylation status of endogenous AMPK and the potential roles of AMPK in mice with lipopolysaccharide (LPS)-induced lethal inflammation. The results indicated that LPS dose-dependently decreased the phosphorylation level of AMPK and its target protein acetyl-CoA carboxylase (ACC). Reactivation of AMPK with the AMPK activator A-769662 suppressed LPS-induced elevation of interleukin 6, alleviated histological abnormalities in lung and improved the survival of LPS-challenged mice. Treatment with A-769662 restored LPS-induced suppression of autophagy, inhibition of autophagy by 3-MA reversed the beneficial effects of A-769662. Treatment with A-769662 suppressed LPS-induced activation of mammalian target of rapamycin (mTOR), co-administration of mTOR activator abolished the beneficial effects of A-769662, and the suppressive effects of A-769662 on uncoordinated-51-like kinase 1 (ULK1) phosphorylation. Inhibition of ULK1 removed the beneficial effects of A-769662. These data indicated that LPS-induced dephosphorylation of AMPK could result in weakened inhibition of mTOR and repression of ULK1-dependent autophagy, which might potentiate the development of LPS-induced inflammatory injury. These data suggest that pharmacological restoration of AMPK activation might be a beneficial approach for the intervention of inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

Fan

et al. 2018

Front. Immunol.

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“…One possible explanation is selective glioblastoma cell type‐specific metabolism . In another study, the NTU283 TG2 inhibitor was found to reduce TG2‐dependent Akt/mTOR signaling in glioblastoma to suppress inflammatory responses …”

Section: Tg2 In Tumor Typesmentioning

confidence: 99%

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Eckert

2019

Molecular Carcinogenesis

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Transglutaminase 2 (TG2) has emerged as a key cancer cell survival factor that drives epithelial to mesenchymal transition, angiogenesis, metastasis, inflammation, drug resistance, cancer stem cell survival and stemness, and invasion and migration. TG2 can exist in a GTP‐bound signaling‐active conformation or in a transamidase‐active conformation. The GTP bound conformation of TG2 contributes to cell survival and the transamidase conformation can contribute to cell survival or death. We present evidence suggesting that TG2 has a role in human cancer, summarize what is known about the TG2 mechanism of action in a range of cancer types, and discuss TG2 as a cancer therapy target.

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“…NHAs are involved in the development of a variety of neurodegenerative diseases [4]; therefore, studying the mechanism of reactive NHAs is helpful for the development of protective strategies for neurodegenerative diseases induced by central nervous system inflammation. Lipopolysaccharide (LPS) is the main component of Gram-negative endotoxin [5], and it is an effective immune system-activating factor, which is usually used to study inflammation-related diseases [6]. Therefore, in this study, LPS was used to treat NHAs to establish an in vitro LPS-induced NHA injury model.…”

Section: Introductionmentioning

confidence: 99%

Isoflurane Regulates Proliferation, Apoptosis, and Inflammatory Response of Lipopolysaccharide-Induced Human Astrocyte through the miR-206/BDNF Axis

Liu

Wang

Liu

2020

International Journal of Polymer Science

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Objective. To investigate the effect of isoflurane (ISO) on the proliferation, apoptosis, and inflammatory response of lipopolysaccharide- (LPS-) induced normal human astrocytes (NHAs) by regulating the miR-206/BDNF axis. Methods. NHA proliferation activity was measured by MTT; NHA apoptotic rates were measured by Annexin V-FITC/PI; western blotting was used to measure the BDNF expression; ELISA was used to measure the IL-6, IL-1β, and TNF-α expression in NHAs; qPCR was used to measure the expressions of miRNAs that are related to NHAs proliferation and apoptosis; dual-luciferase reporter was constructed to validate the targeting relationship between miR-206 and BDNF. Results. LPS increased the proliferation activity and decreased the apoptosis rate of NHAs which were effectively reversed by the ISO (p<0.05); LPS significantly inhibited the expression of miRNAs related to proliferation and apoptosis in NHAs (p<0.05, p<0.01), whereas ISO significantly increased the expression of miR-206 (p<0.01) by downregulating the expression of BDNF, thus inhibiting NHA proliferation and inflammatory response and enhancing apoptosis. Conclusion. ISO can inhibit the expression of BDNF by upregulating the expression of miR-206, thereby inhibiting the proliferation and inflammatory response of NHAs and promoting its apoptosis.

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Inhibition of tissue transglutaminase attenuates lipopolysaccharide-induced inflammation in glial cells through AKT/mTOR signal pathway

Cited by 5 publications

References 49 publications

Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Isoflurane Regulates Proliferation, Apoptosis, and Inflammatory Response of Lipopolysaccharide-Induced Human Astrocyte through the miR-206/BDNF Axis

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