Abstract：
:Rosiglitazone is a member of the thiazolidinedione family of synthetic peroxisome proliferator-activated receptor (PPAR) agonists. It is a selective ligand of the PPARgamma subtype and functions by regulating the transcription of insulin-responsive genes. A screen of FDA-approved compounds identified rosiglitazone as a novel anti-apoptotic agent in retinal cells both in vitro and in vivo, functioning as a neuroprotectant in response to oxidative and calcium stress. We have found that the likely mechanism of action is via increased protein expression of the antioxidant enzymes superoxide dismutase 2 (SOD-2) and sestrin-1, boosting antioxidant defences. Transcription of both genes appears to be mediated by PPARgamma as their up-regulation is reversed by the PPARgamma antagonist GW9662 and proliferator hormone response elements were found in the putative promoter regions of mouse SOD-2 and sestrin-1. However, further investigation revealed that p53 expression was also induced in response to rosiglitazone and chromatin immunoprecipitation assays confirm that it is a bona fide target of PPARgamma. Furthermore, inhibition of p53 partially blocks the observed increase in SOD-2 and sestrin-1 expression indicating that p53 expression is upstream of both antioxidants. We conclude that rosiglitazone may increase cell survival in retinal diseases and potentially other neuronal diseases in which oxidative stress is a key factor.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Doonan F,Wallace DM,O'Driscoll C,Cotter TGdoi
10.1111/j.1471-4159.2009.05995.xsubject
Has Abstractpub_date
2009-04-01 00:00:00pages
631-43issue
2eissn
0022-3042issn
1471-4159pii
JNC5995journal_volume
109pub_type
杂志文章abstract：:Leptin, the obese gene product, was reported to stimulate prolactin (PRL) secretion, but the neuroendocrine mechanism underlying this hormonal response is largely unknown. Thus, in this study we examined the involvement of several important PRL regulators in the leptin-induced PRL secretion in male rats. Compared with...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01683.x
更新日期：2003-04-01 00:00:00
abstract：:Axonal transport of glycoconjugates was studied in the motoneurons of rat sciatic nerve following injection of [3H]glucosamine into the lumbosacral spinal cord. After varying time intervals, the sciatic nerve was exposed, and two ligatures were tied for collection of materials undergoing anterograde and retrograde tra...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb05551.x
更新日期：1985-10-01 00:00:00
abstract：:Plasma osmolality and the levels of water, taurine, and total amino nitrogen (detected as ninhydrin-positive substances) have been measured in the cerebral cortices of nonpregnant and 19-day pregnant Wistar rats. Plasma osmolality fell by 11 mosmol/kg during pregnancy. Brain water content remained unaltered, but level...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb07328.x
更新日期：1989-07-01 00:00:00
abstract：:Nociception evoked prostaglandin (PG) release in the spinal cord considerably contributes to the induction of hyperalgesia and allodynia. To evaluate the relative contribution of cyclooxygenase-1 (COX-1) and COX-2 in this process we assessed the effects of the selective COX-1 inhibitor SC560 and the selective COX-2 in...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00613.x
更新日期：2001-11-01 00:00:00
abstract：:The neuronal nitric oxide (NO) synthase generates NO from arginine. NO mediates its physiological effects mainly by stimulating the synthesis of cyclic GMP. We have investigated the role of the arginine availability on the NMDA-induced cyclic GMP accumulation in immature rat brain slices. The effect of NMDA was blocke...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71052139.x
更新日期：1998-11-01 00:00:00
abstract：:Cytokines and catecholamines are known to constitute a significant portion of the regulatory neuroimmune networks involved in maintaining homeostasis in the central nervous system (CNS). Although we have already reported an increase in norepinephrine (NE) turnover within the locus coeruleus (LC) at 2 and 4 h after the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03209.x
更新日期：2005-07-01 00:00:00
abstract：:Despite the increasing knowledge of Alzheimer's disease (AD) management with novel pharmacologic agents, most of them are only transiently fixing symptomatic pathology. Currently there is rapid growth in the field of neuroprotective pharmacology and increasing focus on the involvement of mitochondria in this devastati...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2010.06814.x
更新日期：2010-08-01 00:00:00
abstract：:Dendritic trafficking and translation of brain-derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA-mediated knockdown of translin, an RNA-binding protein, impairs KCl-induced dendritic trafficking of BDNF mRNA in cultured hippocampal neu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.07166.x
更新日期：2011-03-01 00:00:00
abstract：:Metabolic alterations in amino acids, high-energy phosphates, and intracellular pH during and after insulin hypoglycemia in the rat brain was studied in vivo by 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. Sequential accumulations of 1H and 31P spectra were obtained from a double-tuned surface coil positi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb08723.x
更新日期：1985-04-01 00:00:00
abstract：:Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse mod...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14116
更新日期：2017-09-01 00:00:00
abstract：:We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intrav...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752392.x
更新日期：2000-12-01 00:00:00
abstract：:Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation, which accumulates in the brain during neurodegenerative disorders. Prior to determining Lf function in pathological brain tissues, we investigated its transport through the blood-brain barrier (BBB) in infla...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0732491.x
更新日期：1999-12-01 00:00:00
abstract：:The expression of inducible nitric oxide synthase (NOS2) in glial cells is inhibited by neurotransmitters such as norepinephrine (NE) which elevate cAMP levels. We examined the molecular basis for this effect using a 2.2-kb fragment of the rat NOS2 promoter transfected into rat C6 glioma cells. Promoter activation (up...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00375.x
更新日期：2001-07-01 00:00:00
abstract：:The purpose of the present study was to clarify the expression, transport properties and regulation of ATP-binding cassette G2 (ABCG2) transporter at the rat blood-brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2-transfected HEK293 cells, rABCG2 was detec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02537.x
更新日期：2004-08-01 00:00:00
abstract：:Fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea], a clinically validated non-benzodiazepine anxiolytic, has been shown to be a potent and non-competitive metabotropic glutamate (mGlu)-5 receptor antagonist. In the present study, we have used the site-directed mutagenesis coupled with ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03886.x
更新日期：2006-07-01 00:00:00
abstract：:We have investigated the transport characteristics of dehydroepiandrosterone sulfate (DHEAS), a neuroactive steroid, at the blood-brain barrier (BBB) in a series of functional in vivo and in vitro studies. The apparent BBB efflux rate constant of [(3)H]DHEAS evaluated by the brain efflux index method was 2.68 x 10(-2)...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0751907.x
更新日期：2000-11-01 00:00:00
abstract：:To identify the transductional mechanisms responsible for the neuroprotective effect of nitric oxide (NO) during ischemic preconditioning (IPC), we investigated the effects of this gaseous mediator on mitochondrial Mn-superoxide dismutase (Mn-SOD) expression and activity. In addition, the possible involvement of Ras/e...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04845.x
更新日期：2007-11-01 00:00:00
abstract：:Myelin proteolipid protein (PLP) is known to contain long-chain, covalently bound fatty acids. Previous studies, including our own, have suggested the occurrence of an oxyester type of linkage between fatty acids and PLP. However, we found that protein-SH groups are required in the acylation reaction, suggesting the p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb05786.x
更新日期：1990-12-01 00:00:00
abstract：:The rat glial cell line B49 releases into its culture medium a potent neurotrophic factor that exhibits relative specificity for the dopaminergic neurons in dissociated cultures of rat embryonic midbrain. This factor is a heparin-binding, basic protein that is heterogeneously glycosylated and migrates on sodium dodecy...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63020758.x
更新日期：1994-08-01 00:00:00
abstract：:Patients with cancer cachexia often suffer from psychiatric disorders. In the present study, we investigated the changes in monoaminergic activities in the brain in tumor-bearing mice with reference to the development of cachexia. Two clones, clone-5 (noncachectic clone) and clone-20 (cachectic clone), derived from th...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70010260.x
更新日期：1998-01-01 00:00:00
abstract：:The 5-hydroxytryptamine (serotonin, 5-HT) type 3 (5-HT3) receptor belongs to the superfamily of Cys-loop ligand-gated ion channels, and can be either homopentameric (5-HT3A) or heteropentameric (5-HT3AB) receptor. Several modulators are known, which either inhibit or potentiate this channel, but few have any appreciab...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12146
更新日期：2013-04-01 00:00:00
abstract：:To evaluate the ability of ependymal, microglial and oligodendroglial cells to degrade leucine, the presence of 3-methylcrotonyl-CoA carboxylase (MCC) was investigated in cultures of these cells. MCC is a biotin-containing heterodimeric enzyme that is specific for the irreversible part of the leucine catabolic pathway...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03819.x
更新日期：2006-06-01 00:00:00
abstract：:We studied whether microtubule organization is important for actions of ethanol on GABAA ergic responses by testing the effects of microtubule depolymerization on ethanol enhancement of GABA action in mouse L(tk-) cells stably transfected with GABAA receptor alpha 1 beta 1 gamma 2L subunits. The microtubule-disrupting...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66031318.x
更新日期：1996-03-01 00:00:00
abstract：:To assess maturation of central serotonin and catecholamine pathways at birth, we measured lumbar CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), stable acid metabolites of dopamine and serotonin, using HPLC with electrochemical detection. CSFs from 57 neonates (38 premature and 19 at term) and 13...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb06109.x
更新日期：1984-12-01 00:00:00
abstract：:The axonal outgrowth of cells of Neuro2a, a mouse neuroblastoma cell line, was suppressed on expression of the beta-galactoside alpha 1,2-fucosyltransferase (alpha 1,2-FT) gene. We recently cloned two types of rabbit alpha 1,2-FT, RFT-I and RFT-II. RFT-I exhibits comparable kinetic properties and structural homology w...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66041633.x
更新日期：1996-04-01 00:00:00
abstract：:Genetic factors and nerve injury-induced changes of gene expression in sensory neurons are potential contributors to tactile allodynia, a neuropathic pain state manifested as hypersensitivity to innocuous mechanical stimulation. To uncover genes relevant to neuropathic allodynia, we analyzed gene expression profiles i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02016.x
更新日期：2003-11-01 00:00:00
abstract：:Blood-based tests for the differential diagnosis of Alzheimer's disease (AD) are under intensive investigation and have shown promising results with regard to Abeta40 and Abeta42 peptide species in incipient AD. Moreover, plasma Abeta40 was suggested as an independent cerebrovascular risk factor candidate. These consi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04763.x
更新日期：2007-10-01 00:00:00
abstract：:Incorporation of [1-14C]palmitic acid into neutral lipids and phospholipids of rat cerebral cortex was examined in vitro in normal Krebs--Ringer bicarbonate buffer containing 3% (wt/vol) albumin and 0.75 mM palmitic acid. Under standard assay conditions, radioactivity in the triacylglycerol fraction increased rapidly ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb07914.x
更新日期：1982-05-01 00:00:00
abstract：:Intracerebral administration of [3H]arachidonic acid ([3H]ArA) into 19-20-day-old rat embryos, resulted in a rapid incorporation of label into brain lipids. One hour after injection, 55.6 +/- 8.2, 18.0 +/- 3.4, and 13.7 +/- 1.3% of the total radioactivity was associated with phosphatidylcholine, phosphatidylinositol, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb11014.x
更新日期：1992-11-01 00:00:00
abstract：:Vinblastine causes alterations in the subcellular distribution of certain proteins synthesized by telencephalon slices. Proteins in various subcellular fractions were separated according to their molecular weight by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radioactive proteins were determined by ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb12492.x
更新日期：1980-07-01 00:00:00
