title: Arginine vasopressin regulated ASCT1 expression in astrocytes from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats.
abstract: In stroke-prone spontaneously hypertensive rats (SHRSP/Izm), ischemia induces swelling of astrocytes, a process that subsequently leads to neuronal death. Following ischemic insult, arginine vasopressin (AVP) can induce edema and l-serine released by astrocytes supports the survival of neuronal cells. The purpose of this study was to examine whether AVP contributed to the regulation of l-serine production following ischemic stroke. Here, we used cultured astrocytes from SHRSP/Izm rats and Wistar Kyoto rats (WKY/Izm) to examine whether AVP changed the production of l-serine and/or altered gene expression levels of the neural amino acid transporter (Slc1a4), 3-phosphoglycerate dehydrogenase (Phgdh) and serine racemase (SRR). Furthermore, using astrocytes from the congenic rat SHRpch1_18 strain having quantitative trait loci (QTL) of stroke, we examined expression of those genes under conditions of hypoxia and reoxygenation (H/R). The expression levels of ASCT1 protein, the genes described above and l-serine levels were determined by Western blotting (WB), RT-PCR, real-time quantitative RT-PCR and HPLC. AVP increased the production of l-serine and the expression of Slc1a4 in WKY/Izm and SHRSP/Izm astrocytes. The production of l-serine and the expression of Slc1a4 were lower in SHRSP/Izm than in WKY/Izm cells. This difference was not seen with Phgdh. In the SHRpch1_18 strain, the expression of Slc1a4 and Phgdh significantly decreased after H/R. AVP-mediated enhanced expression of ASCT1 was blocked by the addition of bumetanide. These results suggest that the AVP-mediated attenuated expression of ASCT1 in astrocytes is associated with reduced l-serine production in SHRSP/Izm astrocytes. We hypothesize that reduction of gene expression by AVP might be related to the induction of stroke in the SHRpch1_18 rat strain.
authors.affiliation: Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University (NUBS), Japan; Advance Research Center on Food Function, College of Bioresource Science, NihonUniversity (NUBS), Japan. Electronic address: kyamagat@brs.nihon-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University (NUBS), Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Institute of Experimental Animals, Shimane University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Functional Pathology, Shimane University Faculty of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohara
authors.affiliation: Department of Functional Pathology, Shimane University Faculty of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nabika
mesh_terms: D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000473:pathology*; D002034:Bumetanide / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D020521:Stroke / Q000378:metabolism / Q000473:pathology*
chemical_list: D026962:Amino Acid Transport System ASC; C420504:Slc1a4 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D001127:Arginine Vasopressin
keywords: SHRSP; astrocytes; l-serine