title: Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-κB activation-mediated nitric oxide formation.
abstract: 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-κB 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-κB mediated iNOS-derived NO accumulation.
authors.affiliation: School of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China. jy2006hldai@sohu.com.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China. jiaguizhi2006@163.com.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Orthopedics, First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Liang
authors.affiliation: School of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Han
authors.affiliation: School of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Orthopedics, First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China. meixifan1971@163.com.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019833:Genistein / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D000641:Ammonia; D019833:Genistein
keywords: Ammonia; Astrocyte swelling; Genistein; NF-κB; No; iNOS