Synaptosomal Uptake of Alpha-Ketoglutarate and Glutamine in Thioacetamide-Induced Hepatic Encephalopathy in Rats |
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Authors: | Albrecht Jan Waskiewicz Jolanta Dolinska Monika Rafalowska Urszula |
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Institution: | (1) Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawinskiego St. 5, 02-106 Warsaw, Poland;(2) Department of Neurochemistry, Laboratory of Pathobiochemistry of CNS, Medical Research Centre, Polish Academy of Sciences, Poland |
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Abstract: | The kinetics of uptake of two astroglia-derived glutamate (GLU) precursors, α-ketoglutarate (α-KG) and glutamine (GLN) were
determined in synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide
(TAA). TAA treatment increased by 33% Vmax for high affinity, low capacity α-KG uptake, without influencing its Km. The increase
of the uptake capacity for α-KG may represent a response of the GLUergic nerve terminals to the decreased cerebral α-KG content,
which during HE is associated with depressed activity of pyruvate carboxylase, an enzyme that replenishes α-KG in astrocytes.
The result is thus consistent with the notion that HE affects the astroglial control of GLUergic neurotransmission. The Km
and Vmax for the low affinity, high capacity GLN uptake was not affected by TAA treatment. |
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Keywords: | Thioacetamide hepatic encephalopathy glutamine α -ketoglutarate uptake synaptosomes |
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