title: Chronic hyperammonemia alters protein phosphorylation and glutamate receptor-associated signal transduction in brain.
abstract: There is substantial evidence that hyperammonemia is one of the main factors contributing to the neurological alterations found in hepatic encephalopathy. The mechanisms by which chronic moderate hyperammonemia affects brain function involves alterations in neurotransmission at different steps. This article reviews the effects of hyperammonemia on phosphorylation of key brain proteins involved in neurotransmission (the microtubule-associated protein (MAP-2), Na+/K+-ATPase and NMDA receptors). The physiological function of these proteins is modulated by phosphorylation and its altered phosphorylation in hyperammonemia may contribute to impairment of neurotransmission. The effects of chronic hyperammonemia on signal transduction pathways associated to glutamate receptors, such as the glutamate-nitric oxide (NO)-cGMP pathway, are also reviewed. The possible contribution of the impairment of this pathway in brain in vivo to the neurological alterations present in patients with hepatic encephalopathy is discussed.
authors.affiliation: Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, FVIB, Amadeo de Saboya, 4, 46010, Valencia, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Corbalán
authors.forename: Mariluz
authors.initials: M
authors.lastname: Hernández-Viadel
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Carmina
authors.initials: C
authors.lastname: Montoliu
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate