scholarly journals Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Yu Deng ◽  
Zhao-Fa Xu ◽  
Wei Liu ◽  
Bin Xu ◽  
Hai-Bo Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Rat Cerebral Cortex ◽  
Control Group ◽  
Oxygen Species ◽  
Protein Levels ◽  
Glutamate Transporter 1 ◽  
Hg Accumulation

Objective. This study was to evaluate the effect of riluzole on methylmercury- (MeHg-) induced oxidative stress, through promotion of glutathione (GSH) synthesis by activating of glutamate transporters (GluTs) in rat cerebral cortex.Methods. Eighty rats were randomly assigned to four groups, control group, riluzole alone group, MeHg alone group, and riluzole + MeHg group. The neurotoxicity of MeHg was observed by measuring mercury (Hg) absorption, pathological changes, and cell apoptosis of cortex. Oxidative stress was evaluated via determining reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDAs), carbonyl, sulfydryl, and GSH in cortex. Glutamate (Glu) transport was studied by measuring Glu, glutamine (Gln), mRNA, and protein of glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1).Result. (1) MeHg induced Hg accumulation, pathological injury, and apoptosis of cortex; (2) MeHg increased ROS, 8-OHdG, MDA, and carbonyl, and inhibited sulfydryl and GSH; (3) MeHg elevated Glu, decreased Gln, and downregulated GLAST and GLT-1 mRNA expression and protein levels; (4) riluzole antagonized MeHg-induced downregulation of GLAST and GLT-1 function and expression, GSH depletion, oxidative stress, pathological injury, and apoptosis obviously.Conclusion. Data indicate that MeHg administration induced oxidative stress in cortex and that riluzole could antagonize this situation through elevation of GSH synthesis by activating of GluTs.

scholarly journals Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia

2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Flavia A. Tejeda-Bayron ◽  
David E. Rivera-Aponte ◽  
Christian J. Malpica-Nieves ◽  
Gerónimo Maldonado-Martínez ◽  
Héctor M. Maldonado ◽  
...  
Keyword(s):  
Infarct Size ◽  
Glutamate Transporter ◽  
Triphenyltetrazolium Chloride ◽  
Stroke Outcomes ◽  
Female Mice ◽  
Protein Levels ◽  
Translational Activator ◽  
Glutamate Transporter 1 ◽  
Sensorimotor Performance

Stroke is one of the leading causes of long-term disability. During ischemic stroke, glutamate is released, reuptake processes are impaired, and glutamate promotes excitotoxic neuronal death. Astrocytic glutamate transporter 1 (GLT-1) is the major transporter responsible for removing excess glutamate from the extracellular space. A translational activator of GLT-1, LDN/OSU 0212320 (LDN) has been previously developed with beneficial outcomes in epileptic animal models but has never been tested as a potential therapeutic for ischemic strokes. The present study evaluated the effects of LDN on stroke-associated brain injury. Male and female mice received LDN or vehicle 24 h before or 2 h after focal ischemia was induced in the sensorimotor cortex. Sensorimotor performance was determined using the Rung Ladder Walk and infarct area was assessed using triphenyltetrazolium chloride staining. Males treated with LDN exhibited upregulated GLT-1 protein levels, significantly smaller infarct size, and displayed better sensorimotor performance in comparison to those treated with vehicle only. In contrast, there was no upregulation of GLT-1 protein levels and no difference in infarct size or sensorimotor performance between vehicle- and LDN-treated females. Taken together, our results indicate that the GLT-1 translational activator LDN improved stroke outcomes in young adult male, but not female mice.

scholarly journals mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yiru Xia ◽  
Mengjun Sun ◽  
Yufeng Xie ◽  
Rong Shu
Keyword(s):  
Oxidative Stress ◽  
Poor Response ◽  
Control Group ◽  
Oxygen Species ◽  
Gingival Fibroblasts ◽  
Periodontal Pathogens ◽  
Mtor Inhibition ◽  
Mechanistic Target Of Rapamycin ◽  
Beta Galactosidase

The aging periodontium may be vulnerable to periodontal pathogens and poor response to inflammation and susceptible to tumorigenesis. Human gingival fibroblasts (hGFs) through continuously replicative culture served as an in vitro surrogate for aging. To investigate the effects of the mechanistic target of rapamycin (mTOR) inhibition on the aging gingiva, we stimulated the high-passage hGFs with rapamycin (20 nmol/L) for 3 days and 30 days. The cellular and biological changes were examined by immunofluorescence, real-time PCR, ELISA, Western blotting, and flow cytometry. The data demonstrated that the inhibition of mTOR signaling led to fewer senescence-associated beta-galactosidase- (SA-β-Gal-) positive cells, delayed the onset of senescence, preserved the capability of proliferation, and lowered the expression levels of relevant senescence-associated markers, such as p16INK4a, p21CIP1a, interleukin-6 (IL-6), and IL-8. In addition, when infected by prominent periodontal pathogens, Porphyromonas gingivalis (ATCC 33277), rapamycin-pretreated groups decreased the expression of inflammatory cytokines (IL-6 and IL-8) compared with the control group. mTOR inhibition upregulated the gene expression of antioxidant components (Cat, Sod2, and Prdx3; P<0.05) and consequently neutralized the excessive reactive oxygen species (ROS). In conclusion, our results indicated that mTOR inhibition might rejuvenate the aging gingiva to some extent and relieve inflammation through eliminating oxidative stress.

Effect of Modulation of the Astrocytic Glutamate Transporters’ Expression on Cocaine-Induced Reinstatement in Male P Rats Exposed to Ethanol

2020 ◽  
Author(s):  
Alaa M Hammad ◽  
Fawaz Alasmari ◽  
Youssef Sari
Keyword(s):  
Locomotor Activity ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Ethanol Exposure ◽  
Ethanol Intake ◽  
Cocaine Exposure ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Lactam Antibiotic ◽  
Glutamate Transporter 1

Abstract Aim Reinforcing properties of ethanol and cocaine are mediated in part through the glutamatergic system. Extracellular glutamate concentration is strictly maintained through several glutamate transporters, such as glutamate transporter 1 (GLT-1), cystine/glutamate transporter (xCT) and glutamate aspartate transporter (GLAST). Previous findings revealed that cocaine and ethanol exposure downregulated GLT-1 and xCT, and that β-lactam antibiotics restored their expression. Methods In this study, we investigated the effect of ampicillin/sulbactam (AMP/SUL) (200 mg/kg, i.p.), a β-lactam antibiotic, on cocaine-induced reinstatement and locomotor activity in male alcohol preferring (P) rats using free choice ethanol (15 and 30%, v/v) and water. We also investigated the effect of co-exposure to ethanol and cocaine (20 mg/kg, i.p.) on GLT-1, xCT and GLAST expression in the nucleus accumbens (NAc) core, NAc shell and dorsomedial prefrontal cortex (dmPFC). Results Cocaine exposure decreased ethanol intake and preference. Cocaine and ethanol co-exposure acquired place preference and increased locomotor activity compared to ethanol-exposed rats. GLT-1 and xCT expression were downregulated after cocaine and ethanol co-exposure in the NAc core and shell, but not in dmPFC. AMP/SUL attenuated reinstatement to cocaine as well attenuated the decrease in locomotor activity and ethanol intake and preference. These effects were associated with upregulation of GLT-1 and xCT expression in the NAc core/shell and dmPFC. GLAST expression was not affected after ethanol and cocaine co-exposure or AMP/SUL treatment. Conclusion Our findings demonstrate that astrocytic glutamate transporters within the mesocorticolimbic area are critical targets in modulating cocaine-seeking behavior while being consuming ethanol.

Supplementation of kaempferol to in vitro maturation medium regulates oxidative stress and enhances subsequent embryonic development in vitro

Zygote ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 59-64
Author(s):  
Yuhan Zhao ◽  
Yongnan Xu ◽  
Yinghua Li ◽  
Qingguo Jin ◽  
Jingyu Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Treated Group ◽  
Control Group ◽  
Oxygen Species

SummaryKaempferol (KAE) is one of the most common dietary flavonols possessing biological activities such as anticancer, anti-inflammatory and antioxidant effects. Although previous studies have reported the biological activity of KAE on a variety of cells, it is not clear whether KAE plays a similar role in oocyte and embryo in vitro culture systems. This study investigated the effect of KAE addition to in vitro maturation on the antioxidant capacity of embryos in porcine oocytes after parthenogenetic activation. The effects of kaempferol on oocyte quality in porcine oocytes were studied based on the expression of related genes, reactive oxygen species, glutathione and mitochondrial membrane potential as criteria. The rate of blastocyst formation was significantly higher in oocytes treated with 0.1 µm KAE than in control oocytes. The mRNA level of the apoptosis-related gene Caspase-3 was significantly lower in the blastocysts derived from KAE-treated oocytes than in the control group and the mRNA expression of the embryo development-related genes COX2 and SOX2 was significantly increased in the KAE-treated group compared with that in the control group. Furthermore, the level of intracellular reactive oxygen species was significantly decreased and that of glutathione was significantly increased after KAE treatment. Mitochondrial membrane potential (ΔΨm) was increased and the activity of Caspase-3 was significantly decreased in the KAE-treated group compared with that in the control group. Taken together, these results suggested that KAE is beneficial for the improvement of embryo development by inhibiting oxidative stress in porcine oocytes.

scholarly journals Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

2010 ◽  
Vol 103 (5) ◽  
pp. 2581-2586 ◽  
Author(s):  
Zhiqiang Chen ◽  
Sharon G. Kujawa ◽  
William F. Sewell
Keyword(s):  
Hearing Loss ◽  
Otoacoustic Emissions ◽  
Excitatory Amino Acid ◽  
Spiral Ganglion ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Acoustic Stimulation ◽  
Noise Induced Hearing Loss ◽  
Glutamate Transporter 1 ◽  
Ganglion Neurons

In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. l-serine- O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 μM for 220 min), TBOA (200 μM for 220 min), or SOS (100 μM for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noise-induced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate- or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation.

scholarly journals Hypertension and diabetes mellitus association to oxidative stress in an elderly population

2018 ◽  
Author(s):  
Aleida Rodríguez-Castañenda ◽  
Katia Leticia Martínez-Gonzáles ◽  
Rosalinda Sánchez-Arenas ◽  
Sergio Sánchez-García ◽  
Israel Grijalva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Elderly Population ◽  
Influential Factor ◽  
Control Group ◽  
Oxygen Species ◽  
Group 12 ◽  
High Prevalence ◽  
Prevalence Of Diabetes Mellitus

AbstractBackgroundMexico City has the highest aging rate in the country, as well as a high prevalence of diabetes mellitus (DM) and arterial hypertension (HT). All three on their own, are known to increase oxidative stress (OE).MethodsFinal groups included 18 patients without DM or HT (control group), 12 with DM, 23 with HT, and 18 with DM and HT. The EO was measured by the quantification of reactive oxygen species (ROS), and by determination of lipid peroxidation.ResultsHAS patients showed increased ROS levels as did men with HAS compared with the respective DM and HT groups. Also, women of the control group showed higher levels of ROS compared with men. HT in an aged population turned out to be the most influential factor for oxidative stress increase while DM had no effect whatsoever.

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