title: Elevated dopamine induces minimal hepatic encephalopathy by activation of astrocytic NADPH oxidase and astrocytic protein tyrosine nitration.
abstract: BACKGROUND
  We previously demonstrated that dopamine (DA) overload may be a key mechanism behind development of minimal hepatic encephalopathy (MHE) in rats. It has been shown that low-grade cerebral oedema and oxidative stress play important roles in the pathogenesis of MHE. In the current study, DA-triggered oxidative injury in cerebral cortex was studied.
  
  
  METHODS
  An MHE rat model was used. DA was injected intracerebroventricularly (i.c.v.) into rats and added to primary cortical astrocytes (PCAs). Immunoblotting, immunoprecipitation and immunostaining were conducted after DA injection.
  
  
  RESULTS
  Cognitive impairment and cerebral edema were observed in MHE rats and rats injected with 10 μg DA. Astrocyte swelling was increased by DA. Astrocytic protein tyrosine nitration (PTN) was induced by DA. DA-induced PTN was insensitive to l-NMMA but was blunted by apocynin, superoxide dismutase, catalase and uric acid. Exposure to DA substantially increased levels of astrocytic NADPH oxidase subunits and induced p47(phox) phosphorylation and reactive oxygen species production but decreased the expression and activity of neuronal-type nitric oxide synthase (nNOS).
  
  
  CONCLUSIONS
  PTN induced by DA, which was attributed to NADPH oxidase and not to nNOS, may alter astrocyte function and thereby contribute to the precipitation of MHE episodes.
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Saidan
authors.initials: S
authors.lastname: Ding
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jianjing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Computer, Wen Zhou Medical University, Wenzhou 325000, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: firstdsdan@hotmail.com.
authors.forename: Qichuan
authors.initials: Q
authors.lastname: Zhuge
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D019255:NADPH Oxidases / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D017382:Reactive Oxygen Species; D019323:omega-N-Methylarginine; D014443:Tyrosine; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D004298:Dopamine
keywords: Dopamine; Minimal hepatic encephalopathy; NADPH oxidase; Protein tyrosine nitration