title: Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy.
abstract: Hepatic 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.
authors.affiliation: Experimental Hepatology and Gastroenterology Laboratory, Research Center of Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil; Department of Pathology, University of Miami School of Medicine and Veterans Administration Medical Center, Miami, FL 33101, USA. Electronic address: renataleke@hotmail.com.
authors.forename: Renata
authors.initials: R
authors.lastname: Leke
authors.affiliation: Experimental Hepatology and Gastroenterology Laboratory, Research Center of Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil.
authors.forename: Thayssa D C
authors.initials: TD
authors.lastname: Escobar
authors.affiliation: Department of Pathology, University of Miami School of Medicine and Veterans Administration Medical Center, Miami, FL 33101, USA.
authors.forename: Kakulavarapu V Rama
authors.initials: KV
authors.lastname: Rao
authors.affiliation: Experimental Hepatology and Gastroenterology Laboratory, Research Center of Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil; Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Themis Reverbel
authors.initials: TR
authors.lastname: Silveira
authors.affiliation: Department of Pathology, University of Miami School of Medicine and Veterans Administration Medical Center, Miami, FL 33101, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Norenberg
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
mesh_terms: D026924:Amino Acid Transport System A / Q000096:biosynthesis* / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006501:Hepatic Encephalopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D026924:Amino Acid Transport System A; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D020033:Protein Isoforms; C486716:Slc38a1 protein, rat; C412568:Slc38a2 protein, rat; C037853:glutamine transport proteins; C403222:system N protein 1
keywords: Chronic hepatic encephalopathy; GABA; Glutamine; Glutamine transporters