Abstract:
:The rate of mitosis of cancer cells is significantly higher than normal primary cells with increased metabolic needs, which in turn enhances the generation of reactive oxygen species (ROS) production. Higher ROS production is known to increase cancer cell dependence on ROS scavenging systems to counteract the increased ROS. Therapeutic options which selectively modulate the levels of intracellular ROS in cancers are likely candidates for drug discovery. Docetaxel (DTX) has demonstrated antitumor activity in preclinical and clinical studies. It is thought that DTX induces cell death through excessive ROS production and increased Ca2+ entry. The Ca2+ permeable TRPM2 channel is activated by ROS. Selenium (Se) has been previously used to stimulate apoptosis for the treatment of glioblastoma cells resistant to DTX. However, the potential mechanism(s) of the additive effect of DTX on TRPM2 channels in cancer cells remains unclear. The aim of this study was to evaluate the effect of combination therapy of DTX and Se on activation of TRPM2 in DBTRG glioblastoma cells. DBTRG cells were divided into four treatment groups: control, DTX (10 nM for 10 h), Se (1 μM for 10 h), and DTX+Se. Our study showed that apoptosis (Annexin V and propidium iodide), mitochondrial membrane depolarization (JC1), and ROS production levels were increased in DBTRG cells following treatment with Se and DTX respectively. Cell number and viability, and the levels of apoptosis, JC1, ROS, and [Ca2+]i, induced by DTX, were further increased following addition of Se. We also observed an additive increase in the activation of the NAD-dependent DNA repair enzyme poly (ADP-ribose) polymerase-1 (PARP-1) activity, which was accompanied by a decline in its essential substrate NAD+. As well, the Se- and DTX-induced increases in intracellular Ca2+ florescence intensity were decreased following treatment with the TRPM2 antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA). Therefore, combination therapy with Se and DTX may represent an effective strategy for the treatment of glioblastoma cells and may be associated with TRPM2-mediated increases in oxidative stress and [Ca2+]i.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Ertilav K,Nazıroğlu M,Ataizi ZS,Braidy Ndoi
10.1007/s12640-019-0009-5subject
Has Abstractpub_date
2019-05-01 00:00:00pages
797-808issue
4eissn
1029-8428issn
1476-3524pii
10.1007/s12640-019-0009-5journal_volume
35pub_type
杂志文章abstract::We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumul...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9787-9
更新日期:2018-01-01 00:00:00
abstract::This commentary serves as an introduction to the magnetic resonance imaging (MRI) technique called diffusion kurtosis imaging (DKI) employed in the study by Arab et al. in the present issue of Neurotoxicology Research. In their study, DKI is employed for longitudinal investigation of a methamphetamine intoxication mod...
journal_title:Neurotoxicity research
pub_type: 评论,杂志文章
doi:10.1007/s12640-019-00100-3
更新日期:2020-01-01 00:00:00
abstract::Mitochondria are the major site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, mitochondria produce most of the reactive oxygen species (ROS) in nucleated cells. Redox and bioenergetic abnormalities have been seen in mitochondria during the onset and progression of neurodegenerative diseases....
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00044-8
更新日期:2019-10-01 00:00:00
abstract::Benzophenone-3 (BP-3), the most widely used UV chemical filter, is absorbed well through the skin and gastrointestinal tract and can affect some body functions, including the survival of nerve cells. Previously, we showed that BP-3 evoked a neurotoxic effect in male rats, but since the effects of this compound are kno...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00163-7
更新日期:2020-03-01 00:00:00
abstract::MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingeste...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9831-9
更新日期:2018-04-01 00:00:00
abstract::The hippocampus plays an important role in memory, mood, and spatial navigation. In the dentate gyrus of the adult hippocampus, in the subgranular zone (SGZ), new cells are generated, which differentiate and mature into new neurons. Cisplatin, a highly effective antineoplastic drug with nephrotoxic and ototoxic side e...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9503-y
更新日期:2015-04-01 00:00:00
abstract::Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microgl...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9696-3
更新日期:2017-05-01 00:00:00
abstract::Cultured rat fibroblasts, monkey kidney tumor cells (line Vero) and murine neuroblastoma cells were exposed to dopamine or dopaminochrome in the presence and absence of ascorbic acid. Ascorbic acid is able to potentiate the toxicity of both dopamine and dopaminochrome for all the tested cells. The toxicity of dopamino...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033278
更新日期:1999-12-01 00:00:00
abstract::Several studies investigated the prognostic role of copeptin in stroke. The aim of this study is to assess copeptin levels in serum, and investigate their associations with risk of recurrent stroke in a 1-year follow-up study in patients with ischemic stroke. In this post hoc analysis, serum levels of copeptin and NIH...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9754-5
更新日期:2017-10-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder imposing great threat to an individual's cognitive capability. Mounting evidence suggests that type 2 diabetes mellitus (T2DM) and AD is closely associated with impaired insulin signalling and glucose metabolism in the brain. Member of the peroxisome proliferato...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00258-1
更新日期:2020-07-18 00:00:00
abstract::Methamphetamine (METH) is an illicit drug that is also neurotoxic. Recent studies suggest that in addition to dopamine terminal degeneration in the striatum, METH causes apoptosis in cortical neurons. Earlier, we showed that c-fos knockout mice are more susceptible to the toxic effects of the drug. In order to identif...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/1029842021000045453
更新日期:2002-11-01 00:00:00
abstract::Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-011-9290-7
更新日期:2012-05-01 00:00:00
abstract::Multiple system atrophy (MSA) is characterized by the formation of oligodendroglial cytoplasmic inclusions (GCIs) consisting of alpha-synuclein filaments. AlphaB-crystallin, a small chaperone protein that binds to unfolded proteins and inhibits aggregation, has been documented in GCIs. We investigated the relative abu...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033778
更新日期:2005-01-01 00:00:00
abstract::Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of B...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9526-z
更新日期:2015-05-01 00:00:00
abstract::Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophr...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033357
更新日期:2006-12-01 00:00:00
abstract::Cellular oxidative stress and energy failure were shown to be involved in Glutamate (L-Glu) neurotoxicity, whereas, acetyl-L-carnitine (ALCAR) and ±DL-α-lipoic acid (LA) are known to be key players in the mitochondrial energy production. To evaluate the effects of the above antioxidants, adult rats were pretreated wit...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9165-3
更新日期:2011-02-01 00:00:00
abstract::One of the authors has incorrect family name spelling in the original article. Michael Ashner should read as Michael Aschner. ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,已发布勘误
doi:10.1007/s12640-019-00153-4
更新日期:2020-03-01 00:00:00
abstract::Reward-related incentive learning involves the acquisition by neutral stimuli of an enhanced ability to elicit approach and other responses. Previous studies have shown that both dopamine (DA) and glutamate (Glu) play critical roles in this type of learning. Signaling molecules are intracellular messengers that partic...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033301
更新日期:2004-01-01 00:00:00
abstract::Neurotrophins are initially synthesized as precursor forms that are cleaved to release C-terminal mature forms that bind to Trk receptors to initiate survival and differentiative responses. Recent studies suggest that the precursor form of NGF (proNGF) acts as a distinct ligand by binding to a receptor complex of p75 ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9054-9
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab')2 fragments of antibodies. Herein, we generated Fab and F(ab')2 fragments of thre...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00124-9
更新日期:2020-03-01 00:00:00
abstract::Aluminum-induced neuronal injury has been implicated in various neurodegenerative disorders. However, the underlying mechanism involved in this pathogenesis still remains unknown. Our present findings demonstrated that chronic aluminum exposure resulted in spatial learning impairment and significantly increased intrac...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-013-9451-y
更新日期:2014-07-01 00:00:00
abstract::Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analy...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9483-y
更新日期:2015-01-01 00:00:00
abstract::Propofol and sevoflurane are commonly used drugs in pediatric anesthesia. Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. Newborn Wistar rats were treated with repeated intraperitoneal injections of propofol or sevoflurane inhalation an...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9063-8
更新日期:2009-08-01 00:00:00
abstract::Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resu...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9554-8
更新日期:2016-01-01 00:00:00
abstract::Impulse control disorders (ICDs) comprise a wide spectrum of abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian treatment. Some ICDs share several essential features with substance use disorders. In this work, we have studied the addiction-related gene ankyrin repe...
journal_title:Neurotoxicity research
pub_type: 杂志文章,多中心研究
doi:10.1007/s12640-014-9504-x
更新日期:2015-04-01 00:00:00
abstract::Neuronal cell death caused by pathophysiological over-activation of glutamate receptors and the subsequent CaII overloading, has been implicated in neurodegeneration after stroke, cerebral trauma and epileptic seizures. Recent findings suggest that certain progesterone metabolites (neurosteroids) such as allopregnanol...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033504
更新日期:2008-05-01 00:00:00
abstract::Cognitive impairment in depression may be one of the more practically important aspects of the illness, responsible for much of its morbidity. It also is at the heart of its psychopathology, may contribute to strategies of treatment, and may give us a more easily quantifiable measure of impaired function to correlate ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033237
更新日期:2006-10-01 00:00:00
abstract::The study shows effects of the nonselective adenosine A1/A2A receptor antagonist caffeine and the selective A2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg)...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9372-1
更新日期:2013-07-01 00:00:00
abstract::The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the peripheral nervous system. For each experiment, both sciatic nerves were used. The evoked compound action potentials of the nerves were monitored for over 48 h as an indication of their ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/10298420290007592
更新日期:2002-02-01 00:00:00
abstract::In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for ca...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9872-8
更新日期:2018-08-01 00:00:00