Astrocyte swelling and protein tyrosine nitration in hepatic encephalopathy.
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome during the course of acute or chronic liver disease. It is functional in nature, potentially reversible and precipitated by rather heterogeneous factors. Current evidence suggests that HE is the consequence of a low grade chronic glial edema with subsequent alterations of glioneuronal communication. Other lines of evidence support a role of NMDA receptor activation and oxidative/nitrosative stress in the pathogenesis of HE. Different HE-precipitating factors, such as ammonia, benzodiazepines, inflammatory cytokines and hyponatremia induce or aggravate astrocyte swelling and additionally increase oxidative/nitrosative stress and protein tyrosine nitration. Recent findings suggest a close interrelation between astrocyte swelling, NMDA receptor signaling, glutamate, oxidative stress and nitric oxide, which may result in mutual amplification of swelling and oxidative stress. Via such an autoamplificatory loop astrocytes may integrate HE-relevant signals triggered by HE-precipitating factors. This review focuses on the involvement of astrocyte swelling in protein tyrosine nitration and potential consequences in the setting of HE.
Häussinger
Dieter
D
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Düsseldorf, Germany. haeussin@uni-duesseldorf.de
Schliess
Freimut
F
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology; D048429:Cell Size; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D009566:Nitrates; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D014443:Tyrosine