JOURNAL OF MEMBRANE BIOLOGY
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2017
·Vol. 250
·期 5
·483-492
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IF 1.696
Chai Ran,Chen Yafei,Yuan Hongbo,Wang Xuzhao,Guo Shuai,Qi Jinlong,Zhang Hailin,Zhan Yong,An Hailong
Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Dysfunction of the CaCCs is implicated in many diseases. Drug discovery targeting at CaCCs has recently become possible with the determination that TMEM16A is the molecular identity of CaCCs. In this study, we demonstrated that resveratrol (RES), a Chinese traditional medicine compound, is a novel activator of TMEM16A. The yellow fluorescence protein quenching assay and measurement of intracellular calcium fluorescence intensity show that RES activates TMEM16A channels in an intracellular Ca 2+ -independent way. The data of inside-out patch clamp revealed that RES dose-dependently activates TMEM16A (EC 50 = 47.92 ± 9.35 μM). Furthermore, RES enhanced the contractions of the ileum of guinea pigs by activating the TMEM16A channel, which indicated that RES might be a promising drug for the treatment of gastrointestinal hypomotility. As RES was able to induce TMEM16A channel activation, TMEM16A can be added to the list of RES drug targets.
研究领域:
药理学
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生理学
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药物发现
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DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2020
·Vol. 52
·期 5
·563-569
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IF 2.836
Wang Lianqing,Lan Yongting,Du Yanqin,Xiang Xinxin,Tian Wenxiu,Yang Baoye,Li Tao,Zhai Qiaoli
Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation. However, the bone-related function of plastin 1, another family member of plastins, has not been assessed. In this study, we addressed the functional importance of plastin 1 in osteoblasts. We characterized the expression patterns of plastin 1 during osteoblast differentiation and revealed its important role in this process. In both HEK 293T and hFOB1.19 cells, plastin 1 was demonstrated to regulate intracellular Ca2+. Accordingly, we revealed that higher Ca2+ concentration promotes osteoblast differentiation. Finally, we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency. Together, our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+. Our work sheds new light on the role played by plastins in bone homeostasis.
研究领域:
骨骼生物学
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细胞生理学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2021
·Vol. 35
·期 6
·3181-3193
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IF 5.882
Rui Liu,Shiling Hu,Yuanyuan Ding,Jue Wang,Yuejin Wang,Jiapan Gao,Langchong He
Anaphylactoid reactions are potentially fatal allergic diseases caused by mast cells (MCs), which release histamine and lipid mediators under certain stimuli. Therefore, there is an urgent need to develop new drug candidates to treat anaphylactoid reactions. The MrgX2 receptor mediates anaphylactoid reactions that cause inflammatory diseases. Cortex dictamni is a Chinese herb used for treating allergy-related diseases; however, its active compound is still unknown and its mechanism of action has not yet been reported. The aim of this study was to screen the anti-anaphylactoid compound from C . dictamni extracts. An MrgX2/CMC-HPLC method was established for screening MrgX2-specific compounds retained from the alcohol extract of C . dictamni . A mouse model of hindpaw extravasation was used to evaluate the anti-anaphylactoid effect of this ingredient. Intracellular Ca 2+ mobilization was assessed using a calcium imaging assay. Enzyme immunoassays were performed to measure cytokine and chemokine release levels. The molecular signaling pathways were explored by western blotting. As a result, dictamnine was identified as an effective compound using the MrgX2/CMC method, which remarkably suppressed MC intracellular Ca 2+ mobilization and the release of de novo degranulated substances, and inhibited PKC-PLCγ-IP3R-associated protein signaling molecules. Hence, dictamnine is a novel therapeutic candidate for anaphylactoid reactions via MrgX2.
研究领域:
药理学
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免疫学
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中药学
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分子生物学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
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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
LIFE SCIENCES
·
2024
·
IF 5.2
Fang Chen,Huyan Shen,Gang Liu,Pingping Zhang,Lin Zhang,Siyu Lin,Han Gao,Hong Peng,Yan-Fei Qi,Yan Chen,Yinhui Jiang,Jiandong Huang,Xiangchun Shen,Yu-Si Luo,Ke Zhang
Aims The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. Materials and methods RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca 2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. Key findings Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca 2+ channels and inhibiting virus replication. Significance Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.
研究领域:
药理学
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病毒学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
BRAIN
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2024
·
IF 10.6
Shi Hu-Jiang,Xue Yi-Ren,Shao Hua,Wei Cheng,Liu Ting,He Jie,Yang Yu-Hao,Wang Hong-Mei,Li Na,Ren Si-Qiang,Chang Lei,Wang Zhen,Zhu Li-Juan
The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression.Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist.Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.
研究领域:
神经科学
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药理学
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行为科学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2021
·
IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
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药理学
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分子生物学
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生物化学
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DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 25
·19493-19501
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IF 3.84
Yongchao Mou,Jin Zhou,Fei Xiong,Hong Li,Hongyu Sun,Yao Han,Ning Gu,Changyong Wang
Iron oxide nanoparticles (IRONs) have been widely applied in clinical magnetic resonance imaging and in vitro cardiac tissue engineering. However, the underlying effects of IRONs on the microstructures and biological activity of cardiomyocytes remain a controversial issue. In this study, IRONs were modified with 2,3-dimercaptosuccinic acid (DMSA-IRONs) to increase the hydrophobicity. The effects of DMSA-IRONs on the microstructures and biological activity of cardiomyocytes were systematically investigated. DMSA-IRONs were internalized by cardiomyocytes and mainly distributed in the cytoplasm in a dose-dependent manner. Live/dead assay and MTT assay demonstrated that DMSA-IRONs did not affect the survival of cardiomyocytes. The distribution pattern of F-actin and cell shape were also not changed by the incubation of DMSA-IRONs. Further investigations of the mechanism proved that DMSA-IRONs did not interfere with the formation of cell adherens junctions, gap junctions and intracellular Ca2+ transients of cardiomyocytes. However, the intracellular reactive oxygen species (ROS) concentration in cardiomyocytes with incubation of DMSA-IRONs was significantly reduced due to its peroxidase-like activity. In conclusion, DMSA-IRONs are of good biocompatibility and potentially beneficial for cardiomyocytes by decreasing the intracellular ROS. The study here provides a basic investigation of the DMSA-IRONs application in clinical cell-imaging and cardiac disease therapy.
研究领域:
纳米技术
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心脏病学
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生物医学工程
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细胞生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）