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Kynurenine 3-mono-oxygenase inhibitors attenuate post-ischemic neuronal death in organotypic hippocampal slice cultures 总被引:4,自引:0,他引:4
Carpenedo R Meli E Peruginelli F Pellegrini-Giampietro DE Moroni F 《Journal of neurochemistry》2002,82(6):1465-1471
Kynurenine 3-mono-oxygenase (KMO) inhibitors reduce 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) neosynthesis and facilitate kynurenine metabolism towards kynurenic acid (KYNA) formation. They also reduce tissue damage in models of focal or transient global cerebral ischemia in vivo. We used organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation (OGD) to investigate KMO mechanism(s) of neuroprotective activity. Exposure of the slices to 30 min of OGD caused CA1 pyramidal cell death and significantly decreased the amount of KYNA released in the incubation medium. The KMO inhibitors (m-nitrobenzoyl)-alanine (30-100 micro m) or 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (1-10 micro m) reduced post-ischemic neuronal death and increased KYNA concentrations in slice incubation media. The maximal concentration of KYNA detected in the incubation media of slices treated with KMO inhibitors was approximately 50 nm and was too low to efficiently interact with alpha7 nicotinic acetylcholine receptors or with the glycineb site of N-methyl-d-aspartate (NMDA) receptors. On the other hand, the addition of either 3-HK or QUIN (1-10 micro m) to OGD-exposed hippocampal slices prevented the neuroprotective activity of KMO inhibitors. Our results suggest that KMO inhibitors reduce the neuronal death found in the CA1 region of organotypic hippocampal slices exposed to 30 min of OGD by decreasing the local synthesis of 3-HK and QUIN. 相似文献
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Giuseppina Brasile Laura Mauri Sandro Sonnino Federica Compostella Fiamma Ronchetti 《Amino acids》2013,44(2):435-441
An efficient method for the synthesis of long-chain α,ω-diamino acids, starting from natural α-amino acids, has been developed. The long-chain skeleton has been generated through condensation between a protected aldehyde, derived from l-aspartic acid, and an ylide obtained from an ω-hydroxy-alkyl phosphonium salt. After conversion of the ω-hydroxy group into an amine, catalytic hydrogenation produced the N,N′-protected α,ω-diamino acid. The present route to α,ω-diamino acids allows the modulation of the chain length depending on the length of the ylide used for the Wittig olefination reaction. 相似文献
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Coordinating terminal differentiation with permanent exit from the cell cycle is crucial for proper organogenesis, yet how the cell cycle is blocked in differentiated tissues remains unclear. Important roles for retinoblastoma family proteins and Cyclin-dependent kinase inhibitors have been delineated, but in many cases it remains unclear what triggers cell cycle exit. This review focuses on describing recent advances in deciphering how terminal differentiation and exit from the cell cycle are coordinated. 相似文献
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X-ray crystallographic studies performed on the product of the ketalization reaction of 13beta-ethyl-11alpha-hydroxy-gon-5-ene-3,17-dione have lead to the unequivocal assignment of the 10alpha stereochemistry to C10, showing that an inversion of configuration occurred during formation of the 3,17-diketal. From the Swern oxidation of this compound, 11alpha-(methylthio)methoxy-10alpha-gonene was obtained as the major product instead of the desired 11-ketone. Modeling studies showed that the configurational instability at C10 is determined by the presence of the 11alpha-hydroxyl group. 相似文献
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Growth Arrest‐Specific 6 (GAS6) Promotes Prostate Cancer Survival by G1 Arrest/S Phase Delay and Inhibition of Apoptosis During Chemotherapy in Bone Marrow 下载免费PDF全文