Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy

Abstract

Rama Rao, Kakulavarapu V.; Silveira, Themis Reverbel; Norenberg, Michael D.; and Schousboe, Arne, "Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy" (2015 Keywords:Chronic hepatic encephalopathy Glutamine transporters Glutamine GABA A B S T R A C THepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE. Under physiological conditions, glutamine is fundamental for replenishment of the neurotransmitter pools of glutamate and GABA. The different isoforms of glutamine transporters play an important role in the transfer of this amino acid between astrocytes and neurons. A disturbance in the GABA biosynthetic pathways has been described in bile duct ligated (BDL) rats, a well characterized model of chronic HE. Considering that glutamine is important for GABA biosynthesis, altered glutamine transport and the subsequent glutamate/GABA-glutamine cycle efficacy might influence these pathways. Given this potential outcome, the aim of the present study was to investigate whether the expression of the glutamine transporters SAT1, SAT2, SN1 and SN2 would be affected in chronic HE. We verified that mRNA expression of the neuronal glutamine transporters SAT1 and SAT2 was found unaltered in the cerebral cortex of BDL rats. Similarly, no changes were found in the mRNA level for the astrocytic transporter SN1, whereas the gene expression of SN2 was increased by two-fold in animals with chronic HE. However, SN2 protein immuno-reactivity did not correspond with the increase in gene transcription since it remained unaltered. These data indicate that the expression of the glutamine transporter isoforms is unchanged during chronic HE, and thus likely not to participate in the pathological mechanisms related to the imbalance in the GABAergic neurotransmitter system observed in this neurologic condition.

System N transporters are critical for glutamine release and modulate metabolic fluxes of glucose and acetate in cultured cortical astrocytes: changes induced by ammonia

“…; Leke et al . ). Apart from differences in the techniques used (the use of different antibodies etc.…”

“…It must be noted that discrepant data have been reported regarding expression patterns of system N transporters, and the specific roles of SN1 and SN2 in different animal models [hyperammonemia, HE induced by thioacetamide (TAA), bile duct ligation (BDL) and species (rat vs. mouse)] (Desjardins et al 2012;Rama Rao and Norenberg 2014;Zieli nska et al 2014;Leke et al 2015). Apart from differences in the techniques used (the use of different antibodies etc.…”

Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses

“…COPR5 [ 38 ]) were higher in animals that were eliminated during the endurance competition compared to horses that successfully finished the competition. Additionally, horses that were eliminated during the endurance competition presented higher glutamine and SAT2 expression, which is the transporter responsible for glutamine uptake in the neuronal compartment making them important components of the glutamate/GABA-glutamine cycle [ 39 ]. A study by Keller et al [ 40 ] using 1 H NMR metabolomic analysis of blood from horses with laminitis also showed increased glutamine levels, further pointing to metabolic issues as the underlying cause for elimination in these horses.…”

Ca2+-Permeable Channels/Ca2+ Signaling in the Regulation of Ileal Na+/Gln Co-Transport in Mice

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