Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the CNS, l-serine (l-Ser) plays an essential role in neuronal survival by evoking a variety of biological responses in glial cells. Initially, we examined whether glutamate, hydrogen peroxide (H(2)O(2)), interleukin-1 (IL-1) beta, and sodium nitroprusside (SNP) induce the secretion of l-Ser in astrocytes isolated from Wistar Kyoto rats (WKY). The secretion of l-Ser was significantly induced with glutamate and SNP in cultured astrocytes. Next, to gain insight into the involvement of l-Ser in glutamate-induced neuroprotection, we compared the secretion of l-Ser in astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive rats, WKY. We also examined the mRNA expression of the enzyme that produces l-Ser, 3-phosphoglycerate dehydrogenase (PHGDH), and a neural amino acid transporter, ASCT1, in the cultured astrocytes. A dose-dependent study of glutamate in astrocytes of SHRSP indicated differences in the secretion of l-Ser, and gene expression of PHGDH and ASCT1, compared with levels in the WKY astrocytes. We demonstrated that both the secretion and the gene expression were significantly attenuated in glutamate-treated astrocytes from SHRSP. Cerebral ischemia in SHRSP induced a massive efflux of glutamate, causing delayed neuronal death in region CA1 of the hippocampus. The results suggest that the attenuated secretion of l-Ser in astrocytes is involved in neuronal vulnerability and survival in SHRSP during the production of glutamate, as the secretion of l-Ser, which is stimulated by glutamate, is closely related to the protective effect against glutamate-mediated neurotoxicity. We conclude that glutamate and SNP up-regulate the secretion of l-Ser in primary astrocytes. Secretion of l-Ser is regulated in astrocytes in response to glutamate and nitric oxide and may correspond to the level of l-Ser needed for neuronal survival during brain insults such as ischemic stroke in SHRSP.
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PMID:Glutamate reduces secretion of l-serine in astrocytes isolated from stroke-prone spontaneously hypertensive rats. 1702 64

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.
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PMID:Arginine vasopressin regulated ASCT1 expression in astrocytes from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats. 2461 20