Ephrin/Ephrin Receptor Expression in Ammonia-Treated Rat Astrocytes and in Human Cerebral Cortex in Hepatic Encephalopathy.

Ephrin/Ephrin Receptor Expression in Ammonia-Treated Rat Astrocytes and in Human Cerebral Cortex in Hepatic Encephalopathy.
Neurochem Res. 2014 Jul 27;
Authors: Sobczyk K, Jördens MS, Karababa A, Görg B, Häussinger D
Abstract
Hepatic encephalopathy (HE) represents a neuropsychiatric syndrome, which evolves as a consequence of a low grade cerebral edema and a concomitant oxidative/nitrosative stress response. Ephrin receptors (EphR) and their ligands (ephrins) regulate astrocytic glutamate uptake and gliotransmitter release thereby governing neurotransmission, but their role in HE and ammonia toxicity is unclear. We therefore tested effects of ammonia on expression levels of EphR/ephrin isoforms in cultured rat astrocytes and analysed underlying mechanisms. NH4Cl induced mRNA expression changes of several EphR/ephrin isoforms in a methionine sulfoximine-, NADPH oxidase- and NO synthase-dependent manner in cultured astrocytes. A prominent upregulation was noted for EphR A4 mRNA and protein in NH4Cl-treated astrocytes. NH4Cl-treatment decreased EphR A4 molecular mass to similar extent as found in astrocytes treated with the N-glycosylation inhibitor tunicamycin. Knockdown of EphR A4 by siRNA, or treating astrocytes with NH4Cl or tunicamycin abolished fibroblast growth factor-induced and EphR A4-dependent astrocyte proliferation. NH4Cl-treatment also decreased GLAST mRNA levels in cultured astrocytes. This effect was sensitive to inhi...

Source: Neurochemical Research - July 27, 2014 Category: Neuroscience Authors: Sobczyk K, Jördens MS, Karababa A, Görg B, Häussinger D Tags: Neurochem Res Source Type: research