Abstract:
:Therapy of malignant glioma relies on treatment with the O6 -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O6 -alkylguanine. Since this damage is repaired by O6 -methylguanine-DNA methyltransferase (MGMT), the repair enzyme represents a most important factor of drug resistance, limiting the therapy of malignant high-grade gliomas. Although MGMT has been shown to be transcriptionally up-regulated in rodents following genotoxic stress, it is still unclear whether human MGMT is subject to up-regulation. Here, we addressed the question whether MGMT in glioma cells is enhanced following alkylating drugs or ionizing radiation, using promoter assays. We also checked the response of glioma cell lines to dexamethasone. In a series of experiments, we found no evidence that the human MGMT promoter is significantly up-regulated following treatment with TMZ, the chloroethylating agent nimustine or radiation. It was activated, however, by dexamethasone. Using deletion constructs, we further show that the basal level of MGMT is mainly determined by the transcription factor SP1. The high amount of SP1 sites in the MGMT promoter likely prevents transcriptional up-regulation following genotoxic stress by neutralizing inducible signals. The regulation of MGMT by miRNAs plays only a minor role, as shown by DICER knockdown experiments. Since high dose dexamethasone concomitant with temozolomide is frequently used in glioblastoma therapy, induction of the MGMT gene through glucocorticoids in MGMT promoter unmethylated cases might cause further elevation of drug resistance, while radiation and alkylating drugs seem not to induce MGMT at transcriptional level.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Aasland D,Reich TR,Tomicic MT,Switzeny OJ,Kaina B,Christmann Mdoi
10.1111/jnc.14262subject
Has Abstractpub_date
2018-01-01 00:00:00pages
139-151issue
2eissn
0022-3042issn
1471-4159journal_volume
144pub_type
杂志文章abstract::We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1 affects secretory vesicle exocytosis and quantal release kinetics remain unknown. Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells and...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12086
更新日期:2013-02-01 00:00:00
abstract::In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seiz...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2006.04277.x
更新日期:2007-02-01 00:00:00
abstract::Parkinson's disease (PD) is caused by neuronal cell death. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy, cell death progresses during treatment. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-ox...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05327.x
更新日期:2008-06-01 00:00:00
abstract::Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selectiv...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07597.x
更新日期:2012-03-01 00:00:00
abstract::In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these sub...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.02138.x
更新日期:2004-01-01 00:00:00
abstract::Neuronal nicotinic acetylcholine receptors labelled with tritiated agonists are reduced in the cerebral cortex in Alzheimer's disease (AD), but to date it has not been demonstrated which nicotinic receptor subunits contribute to this deficit. In the present study, autopsy tissue from the temporal cortex of 14 AD cases...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0731635.x
更新日期:1999-10-01 00:00:00
abstract::This article reports the results of a systematic investigation of the different types of antibodies produced in the course of a long-term immunization of rats with mouse nerve growth factor (NGF). We have characterized three types of monoclonal antibodies, namely: (1) antibodies that bind to NGF and inhibit its bindin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb10565.x
更新日期:1988-04-01 00:00:00
abstract::Gliomas are the most common primary malignant brain tumor in adults, but current treatment for glioblastoma multiforme (GBM) is insufficient. Even though glucose is the primary energetic substrate of glioma cells, they are capable of using fatty acids to generate energy. Fatty acid oxidation (FAO) in mitochondria requ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15124
更新日期:2020-07-12 00:00:00
abstract::Nuclei from the cerebral cortices of animals of different ages were separated into neuronal and neuroglial populations. Nuclei from cerebellar neurons were also studied. Using the enzyme micrococcal nuclease as a probe for chromatin structure, we found that the DNA from both neuronal preparations showed a decreased su...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb04769.x
更新日期:1983-08-01 00:00:00
abstract::The herpes simplex virus type 2 (HSV-2) protein ICP10PK has anti-apoptotic activity in virus-infected hippocampal cultures through activation of the Ras/Raf-1/MEK/ERK pathway. To exclude the possible contribution of other viral proteins to cell fate determination, we examined the survival of primary hippocampal cultur...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04745.x
更新日期:2007-10-01 00:00:00
abstract::Treatment with phorbol esters such as 12-O-tetradecanoylphorbol acetate (TPA) rapidly enhances [3H]norepinephrine secretion from digitonin-permeabilized adrenal chromaffin cells. When TPA treatment was prolonged for several hours, a second distinct enhancing effect was observed. This later enhancement was most promine...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb13302.x
更新日期:1990-01-01 00:00:00
abstract::The neurochemical profile of a new compound, Lu 19-005 [(+/-)trans-3-(3,4-dichlorophenyl)-N-methyl-1-indanamine hydrochloride], has been investigated. Lu 19-005 is a potent inhibitor of the synaptosomal uptake of 3,4-dihydroxyphenylethylamine (dopamine, DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT, serotonin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb08803.x
更新日期:1985-05-01 00:00:00
abstract::This Editorial highlights a study by Baglietto-Vargas et al. 2015 published in this issue of J. Neurochem. Stress is one of the environmental factors that can contribute to Alzheimer's disease pathogenesis. However, the role of modern-life stress has not been investigated yet. The authors reveal that modern-life stres...
journal_title:Journal of neurochemistry
pub_type: 评论,社论
doi:10.1111/jnc.13210
更新日期:2015-09-01 00:00:00
abstract::Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cort...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01181.x
更新日期:1988-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12522
更新日期:2014-03-01 00:00:00
abstract::Previous studies have shown that phorbol esters and lithium each stimulate the secretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary tumor cell line AtT20/D16-16. Pretreatment with either lithium or phorbol ester desensitizes the cells to subsequent stimulation by phorbol ester. An early consequenc...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb13133.x
更新日期:1987-01-01 00:00:00
abstract::The proinflammatory cytokine interleukin 1beta (IL-1beta), acting at IL-1R1 receptors, affects neuronal signaling under both physiological and pathophysiological conditions. The molecular mechanism of the rapid synaptic actions of IL-1beta in neurons is not known. We show here that within minutes of IL-1beta exposure,...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03951.x
更新日期:2006-09-01 00:00:00
abstract::Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle ce...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12817
更新日期:2014-11-01 00:00:00
abstract::To test the hypothesis that neuroinflammation contributes to dopaminergic neuron death in the MPTP-lesioned mouse, we compared nigrostriatal degeneration in interleukin (IL)-6 (+/+) with IL-6 (-/-) mice. In the absence of IL-6, a single injection of MPTP (30 mg/kg) resulted in significantly greater striatal dopamine d...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01131.x
更新日期:2002-10-01 00:00:00
abstract::The somatodendritic release of dopamine in substantia nigra previously has been suggested to be nonvesicular in nature and thus to differ from the classical, exocytotic release of dopamine described for the dopaminergic nerve terminal in striatum. We have compared the effects of reserpine, a compound that disrupts ves...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65010192.x
更新日期:1995-07-01 00:00:00
abstract::The aim of this study was to examine the effects of the phorbol ester O-tetradecanoylphorbol 13-acetate (TPA) and forskolin on delta-opioid receptor gene transcription. Treatment of NG108-15 cells with TPA (100 nM) for 48 h increased delta-opioid receptor mRNA levels, whereas different concentrations of forskolin indu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0741355.x
更新日期:2000-04-01 00:00:00
abstract::Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12352
更新日期:2013-09-01 00:00:00
abstract::In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large-conductance voltage- and Ca(2+)-dependent K(+) channels (BK channels) in the release of excitatory and non-excitatory neurotransmitters at hippocampal and non-hippocampal sites has been investi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06938.x
更新日期:2010-10-01 00:00:00
abstract::A naturally occurring point mutation (R231H) within one of the major 3gamma-binding surface (switch II region) on the a subunit of Gs (alpha(s)) has previously been found to disrupt receptor-mediated activation of Gs. The disruption caused by mutating this conserved residue may be a general phenomenon for all a subuni...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::In vitro, the transport of [14C]nicotine into the isolated choroid plexus, the anatomical locus of the blood--CSF barrier, was studied. The isolated rabbit choroid plexus accumulated [14C]nicotine by two processes: an active saturable transport process and a nonsaturable process. The [14C]nicotine accumulation process...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb08669.x
更新日期:1982-02-01 00:00:00
abstract::Serotonin-1A (5-HT(1A) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission. We hypothesized that a decrease in the capacity of 5-HT(1A) receptors to activate G proteins was a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.05201.x
更新日期:2008-05-01 00:00:00
abstract::Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of serine 40 (Ser40). Phosphorylation of serine 40 abolishes the bindi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05509.x
更新日期:2008-08-01 00:00:00
abstract::Muscarinic receptors mediate metabotropic actions of acetylcholine in the CNS and PNS and autocrine functions of acetylcholine in non-neuronal systems. Because of the lack of highly selective muscarinic ligands, the precise location, functional role, and roles in various diseases of the five muscarinic receptor subtyp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2009.06092.x
更新日期:2009-06-01 00:00:00
abstract::Ischemia-induced changes in 31P NMR relaxation were examined in 16 piglets. NMR spectra were acquired under control conditions and during complete cerebral ischemia induced via cardiac arrest. Changes in T1 were assessed directly in six animals during control conditions and after 30-45 min of complete ischemia when ch...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03549.x
更新日期:1993-07-01 00:00:00
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