FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Yihan Yu,Dandan Tian,Sanghyok Ri,Tongchol Kim,Kwangjin Ju,Jiongming Zhang,Shuangshuang Teng,Weixia Zhang,Wei Shi,Guangxu Liu
Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter , plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks . In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa . Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABA A and GABA B receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K + -Cl - cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl − , which was shown to be leveled down to normal by blocking the ionotropic GABA A receptor. Treatment with GABA A receptor antagonist also rescued the suppression of GABA A receptor-associated protein ( GABARAP ), KCC , TNF receptor associated factor 6 ( TRAF6 ), inhibitor of nuclear factor kappa-B kinase subunit alpha ( IKKα ), and nuclear factor kappa B subunit 1 ( NFκB ) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca 2+ , and downregulation of cAMP-dependent protein kinase ( PKA ), calmodulin kinase II ( CAMK2 ), calmodulin ( CaM ), calcineurin ( CaN ), TRAF6 , IKKα , and NFκB . All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABA B receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABA A and GABA B receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.
研究领域:
免疫学
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分子生物学
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海洋生物学
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无脊椎动物生理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Derui Zhang,Xiaonan Wei,Ze Liu,Xiangyun Wu,Changjian Bao,Yuzhe Sun,Nana Su,Jin Cui
Quinoa (Chenopodium quinoa Willd.) with a history of 5000 years as food is extremely rich in nutrients and bioactive compounds, including γ-aminobutyric acid (GABA), a natural four-carbon non-protein amino acid with great benefits to human health. In quinoa, GABA generally increases with the germination time, but the underlying molecular mechanism is unclear. Here, we found that the GABA content in quinoa varied significantly among 25 varieties using an automatic amino acid analyzer. Next, six varieties (three low-GABA and three high-GABA varieties) were used for further analyses. The content of GABA in six varieties all showed an increasing trend after germination. In addition, Pearson’s correlation analysis showed that the changes in GABA content were closely related to the transcript level or enzyme activity of three key enzymes including glutamate decarboxylase (GAD), GABA transaminase (GABA-T), and succinate-semialdehyde dehydrogenase (SSADH) in the GABA shunt, especially GAD. Based on RNA-sequencing analysis, eight GAD genes, two GABA-T genes, one SSADH gene, nine polyamine oxidase (PAO) genes, five diamine oxidase (DAO) genes, four 4-aminobutyraldehyde dehydrogenase (BADH) genes, and three thermospermine synthase ACAULIS5 (ACL5) genes were identified. Among these, CqGAD8 and CqGABA-T2 may make a greater contribution to GABA accumulation during quinoa germination.
研究领域:
植物科学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
Insects
·
2025
·Vol. 16
·期 5
·479
·
IF 2.9
Xiangyi Zhou,Guoxing Chen,Keying Chen,Zhanyi Xu,Jiali Qian,Ru Yan,Bosheng Chen,Huiming Wu,Mengli Chen
Simple SummaryBactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly invasive pest with high transmissibility and adaptability, causes severe damage to various commercial vegetables and fruits. RDL, as the homomeric subunit of γ-aminobutyric acid (GABA) receptors, is the target of several insecticides. In this study, we found thatBdRdlwas highly expressed in the pupae and heads of male and female adult insects. Also, BdRDL was functionally characterized inXenopus oocytesby two-electrode voltage clamping and we found that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Finally, the modeling and molecular docking predicted that fluralaner interacted with BdRDL via hydrogen bonds. These results suggested that fluralaner, as an antagonist of BdRDL, could be used to controlB. dorsalis.Bactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly destructive pest, affects fruits and vegetables globally, leading to significant economic losses. As a homomeric subunit of γ-aminobutyric acid (GABA) receptors, RDL plays a crucial role in various physiological activities in insects. However, functional characterization of RDL fromB. dorsalishas not yet been elucidated. Here, we cloned theRdlgene fromB. dorsalis,BdRdl, and investigated the expression pattern ofBdRdl. The results showed thatBdRdlwas highly expressed in pupae and the heads of male and female adults. Also, we characterized the BdRDL inXenopus oocytesthrough two-electrode voltage clamping. It turned out that the inward current of BdRDL induced by GABA was followed in a dose-dependent manner with a median effective concentration (EC50) of 2.4 × 10−4M. Additionally, we determined the mode action of fluralaner, a new insecticide, on BdRDL in oocytes. We found that fluralaner significantly inhibited the currents induced by GABA, suggesting that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Lastly, the modeling and molecular docking predicted that fluralaner interacted with RDL via hydrogen bonds. Our results not only characterized the RDL ofB. dorsalis, but also revealed that fluralaner works as an antagonist of BdRDL and could be used as an effective strategy forB. dorsaliscontrol.
研究领域:
昆虫学
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分子生物学
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DOI
PubMed
高影响因子
Nature Ecology & Evolution
·
2023
·Vol. 7
·期 9
·1444-1456
·
IF 16.8
Guo Lei,Qiao Xiaomu,Haji Diler,Zhou Tianhao,Liu Zhihan,Whiteman Noah K.,Huang Jia
The molecular mechanisms of coevolution between plants and insects remain elusive. GABA receptors are targets of many neurotoxic terpenoids, which represent the most diverse array of natural products known. Over deep evolutionary time, as plant terpene synthases diversified in plants, so did plant terpenoid defence repertoires. Here we show that herbivorous insects and their predators evolved convergent amino acid changing substitutions in duplicated copies of the Resistance to dieldrin ( Rdl ) gene that encodes the GABA receptor, and that the evolution of duplicated Rdl and terpenoid-resistant GABA receptors is associated with the diversification of moths and butterflies. These same substitutions also evolved in pests exposed to synthetic insecticides that target the GABA receptor. We used in vivo genome editing in Drosophila melanogaster to evaluate the fitness effects of each putative resistance mutation and found that pleiotropy both facilitates and constrains the evolution of GABA receptor resistance. The same genetic changes that confer resistance to terpenoids across 300 Myr of insect evolution have re-evolved in response to synthetic analogues over one human lifespan.
研究领域:
分子生物学
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进化生物学
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昆虫学
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DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Ronghua Peng,Xueyou Qin,Jiawei Lin,Lingyu Wang,Songgu Wu,Junbo Gong
We designed a solvent mixture composed of carboxylic acid solvents and water as the crystallization medium for the selective preparation of three distinct γ-aminobutyric acid (GABA) conformational polymorphs (Form-I, Form-II, and the newly discovered Form-IV). By adjusting the carbon chain length and content of carboxylic acid solvents, we were able to finely tune the solvation environment, leading to the formation of the desired polymorphs. Crash-cooling crystallization experiments demonstrated that with the carbon chain length (C1–C6) and content (0–30%) of carboxylic acid increasing, the polymorphic outcomes gradually change from Form-I to Form-II and ultimately to Form-IV. Interestingly, four different conformations were observed within these three polymorphs. DFT calculation indicated that the stability order of these conformations is conformer-IVβ > conformer-IVα > conformer-II > conformer-I. Based on solution FTIR analysis and solvation free energy calculation, the solvation effect on GABA molecules diminishes with an increasing carbon chain length and content of carboxylic acid solvents. A lower solvation effect makes the desolvation process of GABA molecules much easier so that GABA molecules can undergo sufficient conformational rearrangement during the nucleation stage, thereby adopting a more stable conformation during the molecular assembly process. In this crystallization conditions, Form-IV with a more stable conformation in its crystal structure has the potential to replace Form-II and Form-I through preferential crystallization.
研究领域:
化学
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材料科学
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药物学
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产品关联
DOI
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
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2024
·
IF 3.5
Wang Lingqin,Jia Mengya,Gao Dandan,Li Haixing
The probiotic fermentation of the bioactive substance gamma-aminobutyric acid (GABA) is an attractive research topic. There is still room for further improvement in reported GABA fermentation methods based on a single substrate ( l -glutamic acid or l -monosodium glutamate). Here, we devised a pH auto-buffering strategy to facilitate the fermentation of GABA by Levilactobacillus brevis CD0817. This strategy features a mixture of neutral monosodium l -glutamate plus acidic l -glutamic acid as the substrate. This mixture provides a mild initial pH; moreover, the newly dissolved l -glutamic acid automatically offsets the pH increase caused by substrate decarboxylation, maintaining the acidity essential for GABA fermentation. In this study, a flask trial was first performed to optimize the GABA fermentation parameters of Levilactobacillus brevis CD0817. The optimized parameters were further validated in a 10 L fermenter. The flask trial results revealed that the appropriate fermentation medium was composed of powdery l -glutamic acid (750 g/L), monosodium l -glutamate (34 g/L [0.2 mol/L]), glucose (5 g/L), yeast extract (35 g/L), MnSO 4 ·H 2 O (50 mg/L [0.3 mmol/L]), and Tween 80 (1.0 g/L). The appropriate fermentation temperature was 30 °C. The fermenter trial results revealed that GABA was slowly synthesized from 0–4 h, rapidly synthesized until 32 h, and finally reached 353.1 ± 8.3 g/L at 48 h, with the pH increasing from the initial value of 4.56 to the ultimate value of 6.10. The proposed pH auto-buffering strategy may be popular for other GABA fermentations.
研究领域:
生物技术
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微生物学
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发酵技术
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生物化工
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Si-Yi Han,Hong-Fu Zhao,Zi-Ying Zhao,Jing-Zhi Yu,Ying-Hua Zhang,Zhi-Shen Mu
Food-derived protein peptides with γ-aminobutyric acid transaminase (GABA-T) inhibitory activity possess the promising ability to alleviate anxiety and have become a market focus. This study prepared casein hydrolysate with valid GABA-T inhibitory activity using ultrasound-assisted enzymatic hydrolysis and obtained novel GABA-T inhibitory peptides through isolation and purification. The results demonstrated that ultrasonic pretreatment significantly improved the casein hydrolysis efficiency, enhanced GABA-T inhibitory activity by 19.32%, and allowed retention of 42.37% of the initial inhibitory activity after gastrointestinal digestion. Through peptidomics analysis, five novel GABA-T inhibitory peptides were identified from casein hydrolysate, including FFVAPFPE, VYPFPGPIPN, HLPLPL, FLPYPY, and WQVL (2.79 ± 0.14 to 8.49 ± 0.26 mM). Molecular docking results revealed that these five peptides bind to GABA-T through hydrogen bonds and hydrophobic interactions, with the Arg422 residue potentially serving as the key active site for GABA-T inhibition. This study demonstrates significant potential for both the high-value utilization of casein and the development of antianxiety functional foods targeting GABA-T.
研究领域:
食品科学
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生物化学
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神经药理学
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肽类研究
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酶学
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产品关联
DOI
PubMed
高影响因子
Journal of Fungi
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2025
·Vol. 11
·期 7
·542
·
IF 4
Linhua Cao,Xiaoteng Shi,Tuo Li,Yang Liu,Tuokai Wang,Bozheng Lin,Dongyang Liu,Qirong Shen
Fusaric acid (FSA) is a mycotoxin produced by pathogenicFusariumspecies that inhibits the growth of various beneficial microbes. In this study, we investigated the molecular mechanisms by whichTrichoderma harzianumNJAU4742 (Th), a beneficial fungus, responds to FSA-induced stress. Here, by combining a transcriptome analysis, a gene knockout, and physiological data measurements, our study investigated the molecular mechanisms underlying the response ofTrichoderma harzianumNJAU4742 (Th) to FSA stress. The results showed that FSA can induce severe oxidative stress inTh, and an aldehyde dehydrogenase (Thaldh3) inThplays a critical role in alleviating FSA stress. DeletingThaldh3significantly decreased the γ-aminobutyrate (GABA) content, causing more severe oxidative damage inTh. Furthermore, we also provide evidence demonstrating thatThaldh3alleviates FSA stress by enhancing the activities of key enzymes involved in the tricarboxylic acid cycle and ATP content. A pot experiment showed that an enhanced tolerance to FSA increased theThbiomass, strengthening its antagonistic capacity against pathogens and reducing the disease index in tomatoes. In conclusion, these observations provide new insight into the role of beneficial microbes in promoting plant health.
研究领域:
微生物学
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植物病理学
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生物化学与分子生物学
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环境微生物学
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农业科学
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DOI
PubMed
高影响因子
Metabolites
·
2025
·Vol. 15
·期 3
·175
·
IF 3.7
Liang Chen,Jiaxin Li,Chengwei Fang,Jiepeng Wang
Background/Objectives: Epilepsy is a common chronic and recurrent neurological disorder that poses a threat to human health, andAcorus tatarinowiiSchott (ATS), a traditional Chinese medicine, is used to treat it. This study aimed to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in epilepsy was preliminarily explored, combined with network pharmacology. Methods: An epileptic model of rats was established using pentylenetetrazol. The potential targets and pathways of ATS were predicted by network pharmacology. Ultra Performance Liquid Chromatography–Quadrupole–Time of Flight Mass Spectrometrynce Liquid Chromatography–Quadrupole–Time of Flight Mass Spectrometryance Liquid Chromatography–Quadrupole–Time of Flight Mass Spectrometry and statistical analyses were used to profile plasma metabolites and identify ATS’s effects on epilepsy. Results: Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that ATS was involved in regulating multiple signaling pathways, mainly including the neuroactive ligand–receptor interaction and GABAerGamma-aminobutyrate transaminaseAminobutyrate Transaminaseapse signaling pathway. ATS treatment restored 19 metabolites in epiGamma-aminobutyrate transaminaseminobutyrate Transaminase rats, affecting lysine, histidine, and purine metabolism. GABA-T was found as a new key target for treating epilepsy with ATS. The IC50of ATS for inhibiting GABA-T activity was 57.9 μg/mL. Through metabolomic analysis, we detected changes in the levels of certain metabolites related to the GABAergic system. These metabolite changes can be correlated with the targets and pathways predicted by network pharmacology. One of the limitations of this study is that the correlation analysis between altered metabolites and seizure severity remains unfinished, which restricts a more in-depth exploration of the underlying biological mechanisms. In the future, our research will focus on conducting a more in-depth exploration of the correlation analysis between altered metabolites and seizure severity. Conclusions: These results improved our understanding of epilepsy and ATS treatment, potentially leading to better therapies. The identification of key metabolites and their associated pathways in this study offers potential novel therapeutic targets for epilepsy. By modulating these metabolites, future therapies could be designed to better manage the disorder. Moreover, the insights from network pharmacology can guide the development of more effective antiepileptic drugs, paving the way for improved clinical outcomes for patients.
研究领域:
神经科学
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中药学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Tingting Li,Bingbing Luo,Xiaozhou Zou,Jiamin Yin,Shuyi Lv,Jun Wang,Luchan Gong
γ-Aminobutyric acid (GABA) is a prevalent nonprotein amino acid with diverse physiological functions, attracting considerable interest in the food industry. However, current GABA-producing strains require glutamate as a substrate for synthesis. Probiotics capable of de novo GABA synthesis using sugars without glutamate are crucial for developing novel foods. This study employed a pH indicator method to selectively screen for GABA-producing bacteria. Nineteen strains with fermentation liquid pH greater than 5 were obtained, all demonstrated the ability to synthesize GABA from Daqu . Among these strains, Enterococcus (E.) avium GL1 stood out for its high GABA production capacity, reaching 9.8 g/L when utilizing glucose for de novo GABA synthesis without monosodium glutamate (MSG). E. avium GL1 exhibited robust viability in challenging environments, maintaining stability in simulated gastric and intestinal fluids. As a potentially probiotic strain, E. avium GL1 achieved remarkable GABA production of 206.84 g/L with a production efficiency of 2.87 g/L/h, facilitated by automatic pH control during fermentation through continuous addition of glucose and MSG addition. This exceptional result represents the highest GABA production reported for E. avium , highlighting its significant potential for the development of innovative functional foods.
研究领域:
微生物学
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食品科学
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生物工程
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产品关联
DOI
高影响因子
Journal of Agriculture and Food Research
·
2025
·
IF 6.2
Baolin Han,Weitao Zhou,Rong Fan,Shufan Zhang,Xiaohu Ren,Hucheng Gong,Shulin Tian,Qiang Xu,Minghong Bian
Morus alba 'Seedless Dashi' is an excellent variety with large leaves, which is very suitable for making tea. GABA is an important functional component in mulberry leaf tea, but its role and influence on flavor components and metabolism of mulberry leaf tea are still unclear. In this study, metabolomics methods were used to comprehensively analyze the differences between externally added GABA mulberry leaf tea and non-added GABA mulberry leaf tea. The results showed that GABA treatment significantly increased the total amount and diversity of volatile components of mulberry leaf tea (+38.95%), especially the addition of 6 new pyrazine compounds, which gave mulberry leaf tea nutty and caramel characteristics. Compared with ordinary mulberry tea, 73 different metabolites were screened (65 up-regulated and 8 down-regulated). It was found that GABA tea promotes the accumulation of functional components by regulating amino acid and lipid metabolism pathways. This study provided a theoretical basis for the quality optimization of GABA mulberry leaf tea and confirmed that GABA has the dual role of flavor-enhancing and functional components in mulberry leaf tea.
研究领域:
食品科学
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植物学
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代谢组学
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产品关联
DOI
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 4
·e70208
·
IF 3.4
Wenpu Yao,Junyi Li,Xiaoyan Zhu,Ruiyang Ma,Yunpeng Xu,Ruida Ma,Zihao Guo,Guangqing Mu,Xuemei Zhu
Hypertension is a common chronic disease driven by multiple physiological mechanisms, primarily the overactivation of the renin–angiotensin system (RAS). Gamma-aminobutyric acid (GABA), a nonprotein amino acid, has well-documented health benefits, including antihypertensive and calming effects. This study evaluates the blood pressure-lowering effects of Lactiplantibacillus plantarum DPUL-F233 bacterial powder in spontaneously hypertensive rats (SHRs). The bacterial powder was produced using optimized fermentation and freeze-drying techniques. In the oral administration experiment on SHRs, the group treated with a high dose of bacterial powder via long-term gavage showed a significant reduction in blood pressure compared to the untreated group. Specifically, the final measurements of diastolic and systolic blood pressure were reduced to 206.0 ± 2.35 mm Hg and 145.0 ± 6.78 mm Hg, respectively. The angiotensin-converting enzyme I/Angiotensin II/AT1R axis was downregulated, while the angiotensin-converting enzyme II/Angiotensin 1–7/MasR axis was upregulated, rebalancing the RAS signaling pathway. The high-dose group also demonstrated protective effects on the heart and kidneys, with significant improvements observed in reducing cardiac hypertrophy and kidney damage. Additionally, molecular simulation studies indicated potential inhibition of ACE I by GABA. The results suggest that GABA-rich L. plantarum DPUL-F233 powder has significant potential as a natural antihypertensive supplement, particularly for use in functional food development.
研究领域:
微生物学
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医学
·
营养学
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DOI
PubMed
高影响因子
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