Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-[kappa]B activation-mediated nitric oxide formation

Our previous study has indicated the involvement of epidermal growth factor receptor (EGFR) transactivation in ammonia-induced astrocyte swelling, which represents a major pathogenesis of brain edema in hepatic encephalopathy. In this study, we examined the effect of genistein, a naturally occurred...

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Veröffentlicht in:Metabolic brain disease 2017-06, Vol.32 (3), p.841
Hauptverfasser: Dai, Hongliang, Jia, Guizhi, Wang, Wei, Liang, Chunguang, Han, Siyu, Chu, Minghui, Mei, Xifan
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container_issue 3
container_start_page 841
container_title Metabolic brain disease
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creator Dai, Hongliang
Jia, Guizhi
Wang, Wei
Liang, Chunguang
Han, Siyu
Chu, Minghui
Mei, Xifan
description Our previous study has indicated the involvement of epidermal growth factor receptor (EGFR) transactivation in ammonia-induced astrocyte swelling, which represents a major pathogenesis of brain edema in hepatic encephalopathy. In this study, we examined the effect of genistein, a naturally occurred broad-spectrum protein tyrosine kinase (PTK) inhibitor, on ammonia-induced cell swelling. We found that genistein pretreatment significantly prevented ammonia-induced astrocyte swelling. Mechanistically, ammonia triggered EGFR/extracellular signal-regulated kinase (ERK) association and subsequent ERK phosphorylation were alleviated by genistein pretreatment. Moreover, ammonia-induced NF-[kappa]B nuclear location, iNOS expression, and consequent NO production were all prevented by AG1478 and genistein pretreatment. This study suggested that genistein could alleviate ammonia-induced astrocyte swelling, which may be, at least partly, related to its PTK-inhibiting activity and repression of NF-[kappa]B mediated iNOS-derived NO accumulation.
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subjects Activation analysis
Ammonia
Brain
Cell size
Edema
Enzyme inhibitors
Epidermal growth factor
Epidermal growth factor receptors
Extracellular signal-regulated kinase
Genistein
Hepatic encephalopathy
NF-κB protein
Nitric oxide
Nitric-oxide synthase
Pathogenesis
Phosphorylation
Protein-tyrosine kinase
Swelling
Tyrosine
title Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-[kappa]B activation-mediated nitric oxide formation
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