| RRC ID |
33268
|
| 著者 |
Yamagata K, Yamamoto M, Kawakami K, Ohara H, Nabika T.
|
| タイトル |
Arginine vasopressin regulated ASCT1 expression in astrocytes from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats.
|
| ジャーナル |
Neuroscience
|
| 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.
|
| 巻・号 |
267
|
| ページ |
277-85
|
| 公開日 |
2014-5-16
|
| DOI |
10.1016/j.neuroscience.2014.02.039
|
| PII |
S0306-4522(14)00151-1
|
| PMID |
24613720
|
| MeSH |
Amino Acid Transport System ASC / metabolism*
Animals
Arginine Vasopressin / metabolism*
Arginine Vasopressin / pharmacology
Astrocytes / drug effects
Astrocytes / metabolism*
Brain / pathology*
Bumetanide / pharmacology
Cell Death
Cells, Cultured
Cerebral Cortex / cytology
Chromosomes, Human, Pair 1 / genetics
Chromosomes, Human, Pair 18 / genetics
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics*
Humans
Hypoxia / metabolism
Hypoxia / pathology
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Sodium Potassium Chloride Symporter Inhibitors / pharmacology
Stroke / metabolism
Stroke / pathology*
|
| IF |
3.056
|
| 引用数 |
9
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| ラット |
WKY/Izm(strainID=412)
SHRSP/Izm(strainID=409)
SHR.SHRSP-(D1Rat93-D1Rat269)(D18Rat73-D18Rat11)/Izm(strainID=1082) |
