Decreased glutamate transporter (GLT-1) expression in frontal cortex of rats with acute liver failure.
It has been suggested that reduced astrocytic uptake of neuronally released glutamate contributes to the pathogenesis of hepatic encephalopathy in acute liver failure. In order to further address this issue, the recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failure induced by portacaval anastomosis followed 24 h later by hepatic artery ligation and from appropriate sham-operated controls. GLT-1 expression was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant decrease in expression of transporter protein in the brains of rats with acute liver failure. Reduced capacity of astrocytes to reuptake neuronally released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamate could contribute to the pathogenesis of hepatic encephalopathy and brain edema, two major complications of acute liver failure.
Knecht
K
K
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Michalak
A
A
Rose
C
C
Rothstein
J D
JD
Butterworth
R F
RF
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG