Displaying publications 1 - 20 of 80 in total

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  1. Zhang J, Zhao J, Zuo X, You W, Ru X, Xu F, et al.
    Food Chem, 2024 Jun 15;443:138545.
    PMID: 38306904 DOI: 10.1016/j.foodchem.2024.138545
    The effects of exogenous glutamate treatment on the quality attributes, γ-aminobutyric acid (GABA) shunt, phenylpropanoid pathway, and antioxidant capacity of fresh-cut carrots were investigated. Results showed that glutamate treatment suppressed the increases in lightness and whiteness values, inhibited the degradation of total carotenoids and maintained better flavor and taste in fresh-cut carrots. Moreover, glutamate treatment rapidly promoted the activities of glutamate decarboxylase and GABA transaminase, thus improving the GABA content. It also significantly enhanced the activities of phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate coenzyme A ligase and promoted the accumulation of total phenolics as well as the main individual phenolic compounds, including chlorogenic and caffeic acid. In addition, glutamate application activated the reactive oxygen system-related enzyme including peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase activities to maintain higher antioxidant capacity in fresh-cut carrots. These results demonstrated that exogenous glutamate treatment maintained better nutritional quality and alleviated color deterioration by accelerating the accumulation of GABA and phenolics and enhancing the antioxidant capacity in fresh-cut carrots.
    Matched MeSH terms: Glutamic Acid/metabolism
  2. You W, Zhang J, Ru X, Xu F, Wu Z, Jin P, et al.
    Plant Physiol Biochem, 2024 Jan;206:108217.
    PMID: 38039581 DOI: 10.1016/j.plaphy.2023.108217
    The effect of calcium chloride (CaCl2) treatment on γ-aminobutyric acid (GABA) accumulation in fresh-cut cantaloupe and the involved mechanisms were investigated. The result showed that 1% (w/v) CaCl2 treatment increased GABA content and activities of glutamate decarboxylase (GAD) and succinate semialdehyde dehydrogenase (SSADH), while decreased glutamate (Glu) content and GABA transaminase (GABA-T) activities in fresh-cut cantaloupe. CmCML11 and CmCAMTA5 expressions of CaCl2-treated fruit increased by 187.4% and 165.6% than control fruit in the initial 6 h. Besides, expressions of GABA shunt genes, including CmGAD1, CmGAD2, CmGABA-T and CmSSADH were also up-regulated by CaCl2 treatment during early storage. Moreover, acting as a transcriptional activator, CmCAMTA5 could bind to the CG-box in promoters of CmGAD1, CmGABA-T and CmSSADH and activate their transcription. Furthermore, the interaction between CmCML11 and CmCAMTA5 could enhance the transcriptional activation on GABA shunt genes which were regulated by CmCAMTA5. Collectively, our findings revealed that CaCl2 treatment promoted GABA accumulation in fresh-cut cantaloupe via the combined effect of CmCML11 and CmCAMTA5 in the regulation of expressions of CmGAD1, CmGABA-T, and CmSSADH in GABA shunt.
    Matched MeSH terms: Glutamic Acid
  3. Biria M, Banca P, Healy MP, Keser E, Sawiak SJ, Rodgers CT, et al.
    Nat Commun, 2023 Jun 27;14(1):3324.
    PMID: 37369695 DOI: 10.1038/s41467-023-38695-z
    There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.
    Matched MeSH terms: Glutamic Acid*
  4. Malik JA, Yaseen Z, Thotapalli L, Ahmed S, Shaikh MF, Anwar S
    Mol Biol Rep, 2023 Apr;50(4):3767-3785.
    PMID: 36692676 DOI: 10.1007/s11033-023-08241-7
    Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.
    Matched MeSH terms: Glutamic Acid
  5. Teoh CF, Tuzan AD, Yong AS, Liew KS, Lim LS, Liew HJ
    PeerJ, 2023;11:e15607.
    PMID: 37876908 DOI: 10.7717/peerj.15607
    Intensive research on the effectiveness of chemoattractants has been widely explored to improve the feed qualities in expanding crustacean farming. Taste preferences in slipper lobster remained unknown despite their significant contribution to the lobster fisheries. Chemoattractants allow better performance in aquaculture species by increasing food attractiveness and palatability. Amino acids (AA) have been leading in previous research on crustacean feeding behavior. Given that slipper lobster possesses chemoreceptors to detect and orient towards food, this study investigated an approach to identify the AA with the most potent chemoattractant in eliciting a response from slipper lobster. Behavioral assays were performed to evaluate the responses of slipper lobster Thenus orientalis (carapace length, 52.34 ± 1.52 mm) on 15 crystalline AA and three derivatives of AA (DAA) at three concentrations between 10-1 and 10-3 M as test substances (TS). Meretrix sp. extract was used as a positive control and clean filtered seawater as a negative control. The behavioral responses of 14 T. orientalis were evaluated based on their antennular flicking rate, third maxillipeds activity, and substrate probing by the pereiopods. T. orientalis responded to the solutions of single AA down to a concentration of 10-3 M, excluding histidine and serine. The behavioral activity displayed by T. orientalis increased with the TS concentrations. L-glutamic acid monosodium salt monohydrate, betaine, and glycine solutions elicited the most behavioral responses, whereas histidine exhibited the lowest behavioral responses. Conclusively, L-glutamic acid monosodium salt monohydrate, betaine, and glycine can be potential chemoattractants for T. orientalis.
    Matched MeSH terms: Glutamic Acid
  6. Angelopoulou E, Paudel YN, Julian T, Shaikh MF, Piperi C
    Mol Neurobiol, 2021 Apr;58(4):1372-1391.
    PMID: 33175322 DOI: 10.1007/s12035-020-02201-z
    The exact etiology of Parkinson's disease (PD) remains obscure, although many cellular mechanisms including α-synuclein aggregation, oxidative damage, excessive neuroinflammation, and dopaminergic neuronal apoptosis are implicated in its pathogenesis. There is still no disease-modifying treatment for PD and the gold standard therapy, chronic use of levodopa is usually accompanied by severe side effects, mainly levodopa-induced dyskinesia (LID). Hence, the elucidation of the precise underlying molecular mechanisms is of paramount importance. Fyn is a tyrosine phospho-transferase of the Src family nonreceptor kinases that is highly implicated in immune regulation, cell proliferation and normal brain development. Accumulating preclinical evidence highlights the emerging role of Fyn in key aspects of PD and LID pathogenesis: it may regulate α-synuclein phosphorylation, oxidative stress-induced dopaminergic neuronal death, enhanced neuroinflammation and glutamate excitotoxicity by mediating key signaling pathways, such as BDNF/TrkB, PKCδ, MAPK, AMPK, NF-κB, Nrf2, and NMDAR axes. These findings suggest that therapeutic targeting of Fyn or Fyn-related pathways may represent a novel approach in PD treatment. Saracatinib, a nonselective Fyn inhibitor, has already been tested in clinical trials for Alzheimer's disease, and novel selective Fyn inhibitors are under investigation. In this comprehensive review, we discuss recent evidence on the role of Fyn in the pathogenesis of PD and LID and provide insights on additional Fyn-related molecular mechanisms to be explored in PD and LID pathology that could aid in the development of future Fyn-targeted therapeutic approaches.
    Matched MeSH terms: Glutamic Acid
  7. Wan Nasru WN, Ab Razak A, Yaacob NM, Wan Azman WN
    Malays J Pathol, 2021 Apr;43(1):25-32.
    PMID: 33903302
    INTRODUCTION: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA) receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We, therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls.

    MATERIALS AND METHODS: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine, and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy controls.

    RESULTS: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine, and alanine levels were found in bipolar disorder patients in the manic episode as compared to the healthy controls.

    CONCLUSION: Although the exact relationship between peripheral NMDA receptor co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored and may enlighten some new paths for BD therapy which could reward the patients also clinicians.

    Matched MeSH terms: Glutamic Acid
  8. Akyuz E, Polat AK, Eroglu E, Kullu I, Angelopoulou E, Paudel YN
    Life Sci, 2021 Jan 15;265:118826.
    PMID: 33259863 DOI: 10.1016/j.lfs.2020.118826
    Epilepsy is a neurologicaldisorder characterized by persistent predisposition to recurrent seizurescaused by abnormal neuronal activity in the brain. Epileptic seizures maydevelop due to a relative imbalance of excitatory and inhibitory neurotransmitters. Expressional alterations of receptors and ion channelsactivated by neurotransmitters can lead to epilepsy pathogenesis.

    AIMS: In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy.

    MATERIALS AND METHODS: A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles.

    KEY FINDINGS: Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission.

    SIGNIFICANCE: The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches.

    Matched MeSH terms: Glutamic Acid/metabolism
  9. Hussin FS, Chay SY, Zarei M, Meor Hussin AS, Ibadullah WZW, Zaharuddin ND, et al.
    Foods, 2020 Dec 09;9(12).
    PMID: 33316941 DOI: 10.3390/foods9121826
    The current study evaluated the γ-aminobutyric acid (GABA) producing ability from three novel strains of lactic acid bacteria (L. plantarum Taj-Apis362, assigned as UPMC90, UPMC91, and UPMC1065) co-cultured with starter culture in a yogurt. A combination of UPMC90 + UPMC91 with starter culture symbiotically revealed the most prominent GABA-producing effect. Response surface methodology revealed the optimized fermentation conditions at 39.0 °C, 7.25 h, and 11.5 mM glutamate substrate concentration to produce GABA-rich yogurt (29.96 mg/100 g) with desirable pH (3.93) and water-holding capacity (63.06%). At 2% glucose to replace pyridoxal-5-phosphate (PLP), a cofactor typically needed during GABA production, GABA content was further enhanced to 59.00 mg/100 g. In vivo study using this sample revealed a blood pressure-lowering efficacy at 0.1 mg/kg GABA dosage (equivalent to 30 mg/kg GABA-rich yogurt) in spontaneously hypertensive rats. An improved method to produce GABA-rich yogurt has been established, involving shorter fermentation time and lower glutamate concentration than previous work, along with glucose induction that omits the use of costly PLP, fostering the potential of developing a GABA-rich functional dairy product through natural fermentation with desirable product quality and antihypertensive property.
    Matched MeSH terms: Glutamic Acid
  10. Faridah HS, Goh YM, Noordin MM, Liang JB
    Asian-Australas J Anim Sci, 2020 Dec;33(12):1965-1974.
    PMID: 32164059 DOI: 10.5713/ajas.19.0964
    OBJECTIVE: This study consisted of two stages; the first was to determine the effect of extrusion and sieving treatments on the chemical properties of palm kernel cake (PKC), and accordingly, a follow-up experiment (second stage) was conducted to determine and compare the apparent metabolizable energy (AME), and protein and amino acid digestibility of extruded and sieved PKC.

    METHODS: Two physical treatments, namely extrusion (using temperature profiles of 90°C/100°C/100°C, 90°C/100°C/110°C, and 90°C/100°C/120°C) and sieving (to 8 particles sizes ranging from >8.00 to 0.15 mm) were carried out to determine their effects on chemical properties, primarily crude protein (CP) and fiber contents of PKC. Based on the results from the above study, PKC that extruded with temperature profile 90/100/110°C and of sieved size between 1.5 to 0.15 mm (which made up of near 60% of total samples) were used to determine treatments effect on AME and CP and amino acid digestibility. The second stage experiment was conducted using 64 male Cobb 500 chickens randomly assigned to 16 cages (4 cages [or replicates] per treatment) to the following four dietary groups: i) basal (control) diet, ii) basal diet containing 20% untreated PKC, iii) basal diet containing 20% extruded PKC (EPKC), and iv) basal diet containing 20% sieved PKC (SPKC).

    RESULTS: Extrusion and sieving had no effect on CP and ash contents of PKC, however, both treatments reduced (p<0.05) crude fiber by 21% and 19%, respectively. Overall, extrusion and sieving reduced content of most of the amino acids except for aspartate, glutamate, alanine and lysine which increased, while serine, cysteine and tryptophan remained unchanged. Extrusion resulted in 6% increase (p<0.05) in AME and enhanced CP digestibility (p<0.05) by 32%, as compared to the untreated PKC while sieving had no effect on AME but improved CP digestibility by 39% which was not significantly different from that by extrusion.

    CONCLUSION: Extrusion is more effective than sieving and serves as a practical method to enhance AME and digestibility of CP and several amino acids in broiler chickens.

    Matched MeSH terms: Glutamic Acid
  11. Pui Ping C, Akhtar MN, Israf DA, Perimal EK, Sulaiman MR
    Molecules, 2020 Nov 18;25(22).
    PMID: 33217904 DOI: 10.3390/molecules25225385
    The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.
    Matched MeSH terms: Glutamic Acid
  12. Abu Bakar NA, Sulaiman MR, Lajis N, Akhtar MN, Mohamad AS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S711-S717.
    PMID: 33828366 DOI: 10.4103/jpbs.JPBS_344_19
    Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

    Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.

    Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.

    Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.

    Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

    Matched MeSH terms: Glutamic Acid
  13. Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Biomedicines, 2020 Jul 02;8(7).
    PMID: 32630817 DOI: 10.3390/biomedicines8070191
    The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the "Synaptic Vesicle Cycle" pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
    Matched MeSH terms: Glutamic Acid
  14. Ng SW, Selvarajah GT, Cheah YK, Mustaffa Kamal F, Omar AR
    Pathogens, 2020 May 25;9(5).
    PMID: 32466289 DOI: 10.3390/pathogens9050412
    Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis.

    METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells.

    RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells.

    CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.

    Matched MeSH terms: Glutamic Acid
  15. Kamal H, Tan GC, Ibrahim SF, Shaikh MF, Mohamed IN, Mohamed RMP, et al.
    Front Cell Neurosci, 2020;14:282.
    PMID: 33061892 DOI: 10.3389/fncel.2020.00282
    Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer's and Parkinson's disease.
    Matched MeSH terms: Glutamic Acid
  16. Paudel YN, Othman I, Shaikh MF
    Front Pharmacol, 2020;11:613009.
    PMID: 33732146 DOI: 10.3389/fphar.2020.613009
    Epilepsy is a chronic brain disease afflicting around 70 million global population and is characterized by persisting predisposition to generate epileptic seizures. The precise understanding of the etiopathology of seizure generation is still elusive, however, brain inflammation is considered as a major contributor to epileptogenesis. HMGB1 protein being an initiator and crucial contributor of inflammation is known to contribute significantly to seizure generation via activating its principal receptors namely RAGE and TLR4 reflecting a potential therapeutic target. Herein, we evaluated an anti-seizure and memory ameliorating potential of an anti-HMGB1 monoclonal antibody (mAb) (1, 2.5 and 5 mg/kg, I.P.) in a second hit Pentylenetetrazol (PTZ) (80 mg/kg, I.P.) induced seizure model earlier stimulated with Pilocarpine (400 mg/kg, I.P.) in adult zebrafish. Pre-treatment with anti-HMGB1 mAb dose-dependently lowered the second hit PTZ-induced seizure but does not alter the disease progression. Moreover, anti-HMGB1 mAb also attenuated the second hit Pentylenetetrazol induced memory impairment in adult zebrafish as evidenced by an increased inflection ration at 3 and 24 h trail in T-maze test. Besides, decreased level of GABA and an upregulated Glutamate level was observed in the second hit PTZ induced group, which was modulated by pre-treatment with anti-HMGB1 mAb. Inflammatory responses occurred during the progression of seizures as evidenced by upregulated mRNA expression of HMGB1, TLR4, NF-κB, and TNF-α, in a second hit PTZ group, which was in-turn downregulated upon pre-treatment with anti-HMGB1 mAb reflecting its anti-inflammatory potential. Anti-HMGB1 mAb modulates second hit PTZ induced changes in mRNA expression of CREB-1 and NPY. Our findings indicates anti-HMGB1 mAb attenuates second hit PTZ-induced seizures, ameliorates related memory impairment, and downregulates the seizure induced upregulation of inflammatory markers to possibly protect the zebrafish from the incidence of further seizures through via modulation of neuroinflammatory pathway.
    Matched MeSH terms: Glutamic Acid
  17. Md Nesran ZN, Shafie NH, Md Tohid SF, Norhaizan ME, Ismail A
    PMID: 32280356 DOI: 10.1155/2020/7958041
    In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (-7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71; two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.
    Matched MeSH terms: Glutamic Acid
  18. Wan-Mohtar WAAQI, Ab Kadir S, Halim-Lim SA, Ilham Z, Hajar-Azhari S, Saari N
    Food Sci Biotechnol, 2019 Dec;28(6):1747-1757.
    PMID: 31807347 DOI: 10.1007/s10068-019-00602-y
    In submerged-liquid fermentation, seven key parameters were assessed using one-factor-at-a-time to obtain the highest GABA yield using an industrial soy sauce koji Aspergillus oryzae strain NSK (AOSNSK). AOSNSK generated maximum GABA at 30 °C (194 mg/L) and initial pH 5 (231 mg/L), thus was able to utilize sucrose (327 mg/L of GABA) for carbon source. Sucrose at 100 g/L, improved GABA production at 646 mg/L. Single nitrogen sources failed to improve GABA production, however a combination of yeast extract (YE) and glutamic acid (GA) improved GABA at 646.78 mg/L. Carbon-to-nitrogen ratio (C8:N3) produced the highest cell (24.01 g/L) and GABA at a minimal time of 216 h. The key parameters of 30 °C, initial pH 5, 100 g/L of sucrose, combination YE and GA, and C8:N3 generated the highest GABA (3278.31 mg/L) in a koji fermentation. AOSNSK promisingly showed for the development of a new GABA-rich soy sauce.
    Matched MeSH terms: Glutamic Acid
  19. Harnentis H, Nurmiati N, Marlida Y, Adzitey F, Huda N
    Vet World, 2019 Aug;12(8):1352-1357.
    PMID: 31641319 DOI: 10.14202/vetworld.2019.1352-1357
    Aim: This study aimed at optimizing γ-aminobutyric acid (GABA) production using lactic acid bacteria (LAB) of an Indonesian indigenous fermented buffalo milk (dadih) origin. This study utilized LAB previously cultured from dadih that has the ability to produce GABA.

    Materials and Methods: The study started with the identification of selected LAB by 16S rRNA, followed by optimization of GABA production by culture conditions using different initial pH, temperature, glutamate concentration, incubation time, carbon, and nitrogen sources. 16S rRNA polymerase chain reaction and analysis by phylogenetic were used to identify Lactobacillus plantarum (coded as N5) responsible for the production of GABA.

    Results: GABA production by high-performance liquid chromatography was highest at pH of 5.5, temperature of 36°C, glutamate concentration of 500 mM, and incubation time of 84 h. Peptone and glucose served as the nitrogen and carbon sources, respectively, whereas GABA was produced at optimum fermentation condition of 211.169 mM.

    Conclusion: Production of GABA by L. plantarum N5 was influenced by initial pH of 5.5, glutamic acid concentration, nitrogen source, glucose as carbon source, and incubation temperature and time.

    Matched MeSH terms: Glutamic Acid
  20. Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.
    PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014
    Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.
    Matched MeSH terms: Glutamic Acid/metabolism
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