NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 11
·2890-2903
·
IF 2.472
Han Jun,Zhang Hai,Wang Sheng,Zhou Jun,Luo Yi,Long Li-Hong,Hu Zhuang-Li,Wang Fang,Chen Jian-Guo,Wu Peng-Fei
Sulfhydryl compounds such as dithiothreitol (DTT) and β-mercaptoethanol (β-ME) are widely used as redox agents. Previous studies in our group and other laboratory have reported the effect of sulfhydryl compounds on the function of glutamate receptor, including plasticity. Most of these findings have focused on the N -methyl- d -aspartic acid receptor, in contrast, very little is known about the effect of sulfhydryl compounds on α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). Here, we observed that DTT (100 μM), β-ME (200 μM) and l -cysteine (200 μM) significantly elevated the surface expression of AMPARs via reducing their palmitoylation in rat hippocampal slices in vitro . Increased surface stability of AMPARs was not be correlated with the altered redox status, because the chemical entities containing mercapto group such as penicillamine (200 μM) and 2-mercapto-1-methylimidazole (200 μM) exhibited little effects on the surface expression of AMPARs. Computing results of Asp-His-His-Cys (DHHC) 3, the main enzyme for palmitoylation of AMPARs, indicated that only the alkyl mercaptans with chain-like configuration, such as DTT and β-ME, can enter the pocket of DHHC3 and disrupt the catalytic activity via inhibiting DHHC3 auto-palmitoylation. Collectively, our findings indicate a novel redox-independent mechanism underlay the multiple effects of thiol reductants on synaptic function.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
·
2026
·
IF 31.1
Li Xiaojing,Li Renjie,Wei Yiqing,Chen Jiexin,Zhao Jiaojiao,Zhao Jun,Wang Wei,Li Na,Wang Lili,Hu Tuo,Dong Yanli,Zhu Yongping,Wei Chao,Li Long,Zhang Wei,Huang Zhuo,Zhao Yan
AMPA receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission throughout the central nervous system. Calcium-permeable AMPARs and GluA4-containing receptors are critical for cerebellar functions, such as motor learning, associative memory, auditory processing, and synaptic plasticity. In contrast to the well-characterized, predominantly GluA2-containing AMPARs of the hippocampus and cortex, cerebellar AMPARs contain a higher proportion of GluA4 and remain poorly understood. Here, we generated a highly GluA4-specific antibody. Using this antibody in combination with antibodies specifically recognizing GluA1 and GluA2, we purified native AMPARs and determined the subunit compositions of both calcium-impermeable and calcium-permeable native AMPARs in the cerebellum. The isolated cerebellar AMPARs that contained both GluA1 and GluA4 were calcium-permeable, with GluA4 occupying mainly the B/D positions, GluA1 occupying the A/C positions, and the complex associated primarily with cornichon 3 (CNIH3). We determined the structures of the complex in distinct functional states, including the resting, active, and desensitized states, and characterized the conformational transitions that underlie its activity. During desensitization, the receptor adopts a pseudo-4-fold configuration of the ligand-binding domain layer, which may be important for its functional properties. This study provides a blueprint for the subunit compositions of AMPARs in the cerebellum and clarifies the gating mechanism of the calcium-permeable native AMPAR A1A4 –CNIH3 complex, providing significant insight into AMPAR-mediated synaptic transmission in the cerebellum.
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2026
·
IF 12.2
Yiyi Shu,Biao Zhou,Haoqi Zhang,Xianjing Shi,Furong Guo,Junning Zu,Chuan Liang,Falong Jia,Zhihui Ai
The widespread use of glyphosate (PMG), the most abundant herbicide globally, poses substantial ecological risks owing to the persistence of both PMG and its toxic metabolite, aminomethylphosphonic acid (AMPA). While ubiquitous transition-metal ions strongly influence PMG transformation in water systems, their specific role in the conversion of PMG and AMPA remains insufficiently understood. Here, we reveal that ferrous ions (Fe2+) mediate the sequential transformation and ultimate mineralization of PMG and AMPA by activating molecular oxygen through a dual-chelation mechanism. Initially, Fe2+ chelates the phosphonate group of PMG to form an Fe(II)-PMG complex that activates O2, generating superoxide (O2•–) and oxidizing to Fe(III)-PMG. The resulting O2•– then attacks the C(2)–N of PMG to yield AMPA. Critically, the AMPA intermediate subsequently chelates Fe2+ to form a distinct Fe(II)-AMPA complex that exhibits enhanced O2 activation to O2•– and substantially lowers the energy barrier for C(3)-P cleavage by 0.78 eV. This sustained cycle of complexation and radical generation drives the complete mineralization of PMG to inorganic end products. Our findings elucidate an overlooked pathway─continuous complexation-activated conversion of intermediates─providing new insight into the environmental fate of PMG.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
·
2021
·
IF 19.503
Yingping Huang,Zhangli Li,Kun Yao,Chuncheng Chen,Chaoyuan Deng,Yanfen Fang,Ruiping Li,Hailin Tian
The increasing presence of glyphosate has raised concerns about its potential impact on the environment and human health. The oxidative degradation of glyphosate during biotic and abiotic pathways usually leads to the formation of the toxic and persistent intermediates aminomethylphosphonic acid (AMPA). In this work, we report that the formation of AMPA during the photocatalytic degradation of glyphosate can be determined by its adsorption modes on the photocatalyst. The maximum accumulation of AMPA reached 31% on TiO 2 photocatalyst. However, the formation of AMPA was markedly suppressed in the presence of F – ions, while the production of inorganic species such as PO 4 3– and NO 3 – was largely enhanced. In situ attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectroscopy revealed that the glyphosate was adsorbed on surface of TiO 2 by its phosphate and carboxylate groups, while the adsorption site was changed to its amine group in the presence of F – ions. Such a change in the adsorption mode of glyphosate would facilitate the C–N bonds cleavage in glyphosate molecules, and inhibit the formation of AMPA, which makes the degradation of glyphosate go along a less toxic degradation pathway. The present study reveals a new relationship between the degradation pathway and the adsorption mode of glyphosate, which may also be helpful in other systems of abiotic degradation of glyphosate.
研究领域:
环境科学
·
生物学
✓ 已验证
产品关联
DOI
高影响因子
AIP Advances
·
2024
·Vol. 14
·期 8
·
IF 1.4
Zheng Yu,Song Rujuan,Wei Shengjie,Dong Lei,Chen Yazhou
Long-term potentiation (LTP) in the Schaffer-CA1 region of the hippocampus is closely related to learning and memory. Magnetic stimulation, as an effective physical means of regulating synaptic plasticity, has received widespread attention. However, research on the mechanism of the effect of different frequencies of magnetic fields (MFs) on LTP is relatively scarce. This article focuses on Ca 2+ , Na + , K + , NMDA receptors, and AMPA receptors that play important roles in the process of MF regulation of LTP. A combined electrophysiological and pharmacological approach was used to identify Ca 2+ as a key factor in the modulation of LTP by MFs of different frequencies. Subsequently, further experiments revealed that low levels of intracellular Ca 2+ concentration ([Ca 2+ ] i ) intensified the inhibition of low-frequency MFs on LTP, while high levels of [Ca 2+ ] i enhanced the promotion effect of high-frequency MFs on LTP, indicating a positive correlation between [Ca 2+ ] i levels and MF regulation of LTP levels. The research results of this article may help explore the deeper relationship between different frequencies of MFs and synaptic plasticity, and they also have a certain reference value for magnetic stimulation therapy in the treatment of neurological diseases related to LTP injury or learning and memory deficits.
研究领域:
神经科学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2023
·
IF 8.6
Lei Jin,Yunlong Chen,Hailin Tian,Xiang Liu,Yingping Huang,Ruiping Li,Chuncheng Chen,Zhongxu Dai,Di Huang
The selective cleavage-bond of glyphosate is still a major challenge, especially in biodegradation and chemical degradation like advanced oxidation process (AOP). In this work, we found that the BiVO 4 and BiVO 4 /BiPO 4 heterogeneous photocatalysts generated different intermediates during the photocatalytic degradation of glyphosate. The main intermediate product by the BiVO 4 photocatalyst was aminomethylphosphonic acid (AMPA, reaching to 81%) with high biological toxicity, which means glyphosate was degraded through the AMPA pathway. While the BiVO 4 /BiPO 4 heterogeneous photocatalysts showed a significant inhibition of the accumulated AMPA (31%) at pH = 4, leading to the generation of benign products, such as sarcosine, acetic acid and PO 4 3- . More importantly, the BiVO 4 /BiPO 4 -2 photocatalyst barely generated AMPA (less than 5%) at pH = 10. The lower AMPA concentration in our experiments was not attributed to its rapid degradation rate because AMPA could not be degraded from acidic (pH = 4) to alkaline (pH = 10). It indicated that glyphosate suffered from two cleavage-bond pathways between the BiVO 4 and BiVO 4 /BiPO 4 heterogeneous photocatalysts, which had been proved by mass spectrometry (MS) results. The attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectrum and density function theory (DFT) demonstrated that the adsorption sites of the BiVO 4 /BiPO 4 -2 photocatalyst occurred on the phosphate group of glyphosate molecules at pH = 10, which facilitated the C–P bond cleavage and inhibited the formation of AMPA. We found that pH-mediated BiVO 4 /BiPO 4 dipole controlled and changed glyphosate electron cloud distribution, played an important role in the selective cleavage-bond of glyphosate. These results revealed both scientific and environmental significance for the efficient degradation of glyphosate through benign intermediates in soil and water.
研究领域:
环境科学
·
光催化技术
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 8
·1-20
·
IF 5.638
Yang Qin,Zheng Fangshuo,Hu Yida,Yang Yi,Li Yun,Chen Guojun,Wang Wei,He Miaoqing,Zhou Ruijiao,Ma Yuanlin,Xu Demei,Tian Xin,Gao Xiaoya,Wang Qing,Wang Xuefeng
Epilepsy is one of the most prevalent and drug-refractory neurological disorders. Zinc finger DHHC-type containing 8 (ZDHHC8) is a putative palmitoyltransferase that is highly expressed in the brain. However, the impact of ZDHHC8 on seizures remains unclear. We aimed to explore the association of ZDHHC8 with epilepsy and investigate its in epileptogenesis in in vivo and in vitro models through behavioral, electrophysiological, and pathological studies. We used kainic acid- and pilocarpine-induced C57BL/6 mice and magnesium-free-induced pyramidal neurons as experimental epileptic models in this study. We first found increased ZDHHC8 expression in the brains of temporal lobe epilepsy (TLE) patients, similar to that observed in chronic epileptic mice, strongly suggesting that ZDHHC8 is correlated with human epilepsy. In the in vitro seizure models, knocking down ZDHHC8 using recombinant adeno-associated virus (rAAV) delayed seizure precipitation and decreased chronic spontaneous recurrent seizures (SRSs) and epileptiform-like discharges, while ZDHHC8 overexpression had the opposite effect. ZDHHC8 levels were consistent with seizure susceptibility in induced mice with SRSs. In an in vitro magnesium-free model, neuronal hyperexcitability and hypersynchrony were reduced in ZDHHC8-knockdown neurons but were increased in ZDHHC8-overexpressing neurons. To further explore the potential mechanisms, we observed that ZDHHC8 had a significant modulatory effect on 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-related excitatory, but not inhibitory, glutamatergic synaptic neurotransmission, further affecting the inward rectification of AMPA currents in acute hippocampal slices in whole-cell recordings. ZDHHC8 facilitated GluA1 trafficking to the neuronal surface in the hippocampus, as shown by immunoprecipitation and Western blotting. These results suggest that ZDHHC8 may promote the generation and propagation of seizures in humans and that knocking down ZDHHC8 might produce anti-epileptogenic effects in drug-resistant epilepsy. Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2022
·
IF 6.796
Yunlong Chen,Yingping Huang,Hailin Tian,Liqun Ye,Ruiping Li,Chuncheng Chen,Zhongxu Dai,Di Huang
With increasing concerns on the environment and human health, the degradation of glyphosate through the formation of less toxic intermediates is of great importance. Among the developed methods for the degradation of glyphosate, photodegradation is a clean and efficient strategy. In this work, we report a new photocatalyst by doping F ion on BiVO 4 that can efficiently degrade glyphosate and reduce the toxic emissions of aminomethylphosphonic acid (AMPA) through the selective (P)−C−N cleavage in comparison of BiVO 4 catalyst. The results demonstrate that the best suppression of AMPA formation was achieved by the catalyst of 0.3F@BiVO 4 at pH = 9 (AMPA formation below 10%). In situ attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectroscopy indicates that the adsorption sites of glyphosate on BiVO 4 and 0.3F@BiVO 4 are altered due to the difference in electrostatic interactions. Such an absorption alteration leads to the preferential cleavage of the C−N bond on the N−C−P skeleton, thereby inhibiting the formation of toxic AMPA. These results improve our understanding of the photodegradation process of glyphosate catalyzed by BiVO 4 -based catalysts and pave a safe way for abiotic degradation of glyphosate.
研究领域:
环境科学
·
材料科学
·
催化化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EMBO REPORTS
·
2022
·Vol. 23
·期 10
·e54543
·
IF 9.071
Xuanyue Ma,Liuren Li,Ziming Li,Zhengyi Huang,Yaorong Yang,Peng Liu,Daji Guo,Yueyao Li,Tianying Wu,Ruixiang Luo,Junyu Xu,Wen-Cai Ye,Bin Jiang,Lei Shi
Regulation of mRNA translation is essential for brain development and function. Translation elongation factor eEF2 acts as a molecular hub orchestrating various synaptic signals to protein synthesis control and participates in hippocampus-dependent cognitive functions. However, whether eEF2 regulates other behaviors in different brain regions has been unknown. Here, we construct a line of Eef2 heterozygous (HET) mice, which show a reduction in eEF2 and protein synthesis mainly in excitatory neurons of the prefrontal cortex. The mice also show lower spine density, reduced excitability, and AMPAR-mediated synaptic transmission in pyramidal neurons of the medial prefrontal cortex (mPFC). While HET mice exhibit normal learning and memory, they show defective social behavior and elevated anxiety. Knockdown of Eef2 in excitatory neurons of the mPFC specifically is sufficient to impair social novelty preference. Either chemogenetic activation of excitatory neurons in the mPFC or mPFC local infusion of the AMPAR potentiator PF-4778574 corrects the social novelty deficit of HET mice. Collectively, we identify a novel role for eEF2 in promoting prefrontal AMPAR-mediated synaptic transmission underlying social novelty behavior.
研究领域:
神经科学
·
分子生物学
·
行为科学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2020
·
IF 5.893
Yongzhou Yu,Zuxiao Yang,Baohua Jin,Xia Qin,Xiaoque Zhu,Jiahui Sun,Lifang Huo,Ri Wang,Yongyun Shi,Zhanfeng Jia,Yun Stone Shi,Shifeng Chu,Dezhi Kong,Wei Zhang
Cannabidiol (CBD) is a major phytocannabinoid in Cannabis sativa. CBD is being increasingly reported as a clinical treatment for neurological diseases. Febrile seizure is one of the most common diseases in children with limited therapeutic options. We investigated possible therapeutic effects of CBD on febrile seizures and the underlying mechanism. Use of a hyperthermia-induced seizures model revealed that CBD significantly prolonged seizure latency and reduced the severity of thermally-induced seizures. Hippocampal neuronal excitability was significantly decreased by CBD. Further, CBD significantly reduced the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated evoked excitatory postsynaptic currents (eEPSCs) and the amplitude and frequency of miniature EPSCs (mEPSCs). Furthermore, CBD significantly accelerated deactivation in GluA1 and GluA2 subunits. Interestingly, CBD slowed receptor recovery from desensitization of GluA1, but not GluA2. These effects on kinetics were even more prominent when AMPAR was co-expressed with γ-8, the high expression isoform 8 of transmembrane AMPAR regulated protein (TARPγ8) in the hippocampus. The inhibitory effects of CBD on AMPAR depended on its interaction with the distal N-terminal domain of GluA1/GluA2. CBD inhibited AMPAR activity and reduced hippocampal neuronal excitability, thereby improving the symptoms of febrile seizure in mice. The putative binding site of CBD in the N-terminal domain of GluA1/GluA2 may be a drug target for allosteric gating modulation of AMPAR.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2014
·Vol. 10
·期 1
·248-254
·
IF 1.484
Xianwen Chen,Huang Li,Mingqing Huang,Mei Huang,Wei Xu,Kedan Chu,Lidian Chen,Yuqin Zhang
Gua Lou Gui Zhi decotion (GLGZD) has been reported to be an effective treatment for post‑apoplectic limb spasm in the clinic. The present study aimed to investigate whether GLGZD had an affect on cerebral injuries induced by middle cerebral artery occlusion (MCAO) in rats and its possible mechanism. High‑performance liquid chromatography was performed to analyze GLGZD. Furthermore, a model was established to assess the efficacy of GLGZD. Neurological defect scores and screen tests were analyzed. Brain ischemic infarct volume was measured using 2,3,5‑triphenyl tetrazolium chloride staining and glutamic acid (Glu), aspartic acid (Asp) and glycine (Gly) levels in the cerebrospinal fluid were measured using the Hitachi automatic amino acid analyzer. Immunohistochemistry was performed to determine the expression of the α‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazole‑propionic acid (AMPA) and N‑methyl‑D‑aspartic acid (NMDA) glutamate receptors, and to analyze histopathological change. GLGZD was found to improve neurological performance and reduce infarct volumes in MCAO rats. In addition, GLGZD was observed to enhance motor performance, which was assessed using the screen test. Furthermore, GLGZD was found to reduce Glu, Asp and Gly levels in the cerebrospinal fluid and downregulate the protein expression of the AMPA and NMDA glutamate receptors. Thus, it was demonstrated that GLGZD may exert neuroprotective effects through the modulation of excitatory amino acids, and AMPA and NMDA receptor expression.
研究领域:
神经科学
·
中药学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Mengmeng Tong,Wanjun Gao,Weiting Jiao,Jie Zhou,Yeyun Li,Lili He,Ruyan Hou
The uptake, translocation, metabolism, and distribution behavior of glyphosate in nontarget tea plant were investigated. The negative effects appeared to grown tea saplings when the nutrient solution contained glyphosate above 200 mg L–1. Glyphosate was highest in the roots of the tea plant, where it was also metabolized to aminomethyl phosphonic acid (AMPA). The glyphosate and AMPA in the roots were transported through the xylem or phloem to the stems and leaves. The amount of AMPA in the entire tea plant was less than 6.0% of the amount of glyphosate. The glyphosate level in fresh tea shoots was less than that in mature leaves at each day. These results indicated that free glyphosate in the soil can be continuously absorbed by, metabolized in, and transported from the roots of the tea tree into edible leaves, and therefore, free glyphosate residues in the soil should be controlled to produce teas free of glyphosate.
研究领域:
植物科学
·
环境科学
·
农业
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）