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卫星胶质细胞多巴胺受体-缝隙连接connexins的互作通路

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延安大学学报（医学科学版） 2018年第1期16卷 81-85,89页

作者：曹成慧马绥斌刘霞白占涛延安大学生命科学学院/延安大学多肽资源药物研究中心/陕西省区域生物资源保育利用工程技术研究中心陕西延安716000

卫星胶质细胞是背根神经节中主要胶质细胞类型。多巴胺受体和缝隙连接蛋白connexins是卫星胶质细胞功能的关键分子信号通路之一。本文从结构特点、表达分布、磷酸化调控等方面来综述多巴胺受体-connexins互作的新通路,以拓展卫星胶质细... 详细信息

卫星胶质细胞是背根神经节中主要胶质细胞类型。多巴胺受体和缝隙连接蛋白connexins是卫星胶质细胞功能的关键分子信号通路之一。本文从结构特点、表达分布、磷酸化调控等方面来综述多巴胺受体-connexins互作的新通路,以拓展卫星胶质细胞生理与疾病发生的细胞与分子机制,为基于多巴胺受体和缝隙连connexins相关疾病的多靶点诊治和药物发现提供科学与实践基础。

关键词：背根神经节卫星胶质细胞多巴胺受体 connexins 缝隙连接

Expression of the methylcytosine dioxygenase ten-eleven translocation-2 and connexin 43 in inflammatory bowel disease and colorectal cancer

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World Journal of Gastroenterology 2022年第40期28卷 5845-5864页

作者： Mohammad El-Harakeh Jessica Saliba Kawthar Sharaf Aldeen May Haidar Layal El Hajjar Mireille Kallassy Awad Jana G Hashash Margret Shirinian Marwan El-Sabban Department of Anatomy Cell Biology and Physiological SciencesFaculty of MedicineAmerican University of BeirutBeirut 1107Lebanon UR GPF Laboratory of Biodiversity and Functional Genomics Faculty of ScienceUniversitéSaint-Joseph de BeyrouthBeirut 1107Lebanon Department of Biology Faculty of SciencesLebanese UniversityBeirut 1533Lebanon Department of Public Health Faculty of Health SciencesUniversity of BalamandDekwanehSin el Fil 1552Lebanon Department of Internal Medicine Division of Gastroenterology and HepatologyFaculty of MedicineAmerican University of BeirutBeirut 1107Lebanon Department of Experimental Pathology Immunology and MicrobiologyFaculty of MedicineAmerican University of BeirutBeirut 1107Lebanon

BACKGROUND Inflammatory bowel disease(IBD)constitutes a substantial risk factor for colorectal *** 43(Cx43)is a protein that forms gap junction(GJ)complexes involved in intercellular communication,and its expression is altered under pathological conditions,such as IBD and *** studies have implicated epigenetic processes modulating DNA methylation in the pathogenesis of diverse inflammatory and malignant *** ten-eleven translocation-2(TET-2)enzyme catalyzes the demethylation,hence,regulating the activity of various cancer-promoting and tumor-suppressor *** To investigate Cx43 and TET-2 expression levels and presence of 5-hydroxymethylcytosine(5-hmC)marks under inflammatory conditions both in vitro and in *** TET-2 expression was evaluated in parental HT-29 cells and in HT-29 cells expressing low or high levels of Cx43,a putative tumor-suppressor gene whose expression varies in IBD and colorectal cancer,and which has been implicated in the inflammatory process and in tumor *** dextran sulfate sodium-induced colitis model was reproduced in BALB/c mice to evaluate the expression of TET-2 and Cx43 under inflammatory conditions in *** addition,archived colon tissue sections from normal,IBD(ulcerative colitis),and sporadic colon adenocarcinoma patients were obtained and evaluated for the expression of TET-2 and *** levels were reported at the transcriptional level by quantitative real-time polymerase chain reaction,and at the translational level by Western blotting and *** Under inflammatory conditions,Cx43 and TET-2 expression levels increased compared to noninflammatory ***-2 upregulation was more pronounced in Cx43-deficient ***,colon tissue sections from normal,ulcerative colitis,and sporadic colon adenocarcinoma patients corroborated that Cx43 expression increased in IBD and decreased in adenocarcinoma,compared to tissues from non-IBD ***,TET-2

关键词： Demethylation Inflammation-induced carcinogenesis Ulcerative colitis Colorectal cancer connexins

Astrocytic modulation of potassium under seizures

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Neural Regeneration Research 2020年第6期15卷 980-987页

作者： Fushun Wang Xiaoming Qi Jun Zhang Jason HHuang Department of Neurosurgery Baylor Scott&White HealthTempleTXUSA Institute of Brain and Psychological Science Sichuan Normal UniversityChengduSichuan ProvinceChina Department of Neurosurgery PLA General HospitalBeijingChina Department of Surgery Texas A&M University College of MedicineTempleTXUSA

The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellular K^+ concentration([K^+]o).When[K^+]o reaches peaks of 10-12 mM,it is strongly associated with seizure initiation during hypersynchronous neuronal *** the other hand,reactive astrocytes during a seizure attack restrict influx of K^+ across the membrane both passively and *** addition to decreased K^+ buffering,aberrant Ca^2+ signaling and declined glutamate transport have also been observed in astrogliosis in epileptic specimens,precipitating an increased neuronal discharge and induction of *** review aims to provide an overview of experimental findings that implicated astrocytic modulation of extracellular K^+ in the mechanism of epileptogenesis.

关键词： AQP4 Ca^2+ signaling cell volume connexins epilepsy K^+ buffering mi RNA NKCC pannexin TBI

The relationship between gap junctional remodeling and human atrial fibrillation

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Chinese Medical Journal 2004年第8期117卷 1256-1258页

作者：李大强冯义柏张会琴 Department of Cardiology The Union Hospital TongJi Medical CollegeHuaZhong Science & Technology UniversityWuhan430022China

Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF.1 The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of (connexin 40, Cx 40) and (connexin 43, Cx 43) in the right atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.

关键词： atrial fibrillation gap junctional remodeling connexins

Modulation of Cx43 phosphorylation underlying mirror image pain

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Modulation of Cx43 phosphorylation underlying mirror image p...

中国神经科学学会第十二届全国学术会议

作者： Jia Li Qi Wang Huan Guo Dan-Yang Li Xu-Ri Zhang Rui Gao Ruo-Song Ai Qing-Hu Yang Cheng-Hui Cao Sui-Bin Ma Yan-Yan Wu Xiang-Xiang Chen Lei Xi Zhan-Tao Bai College of Life Sciences Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources

Gap junctions（GJ） play an important role in intercellular communication between adjacent cells. The protein expression, membrane cluster, subtype couple, pore selectivity and gating of GJs might be regulated by phosphorylation of connexins. Combining with behavioral observation, quantitative real-time PCR, immunoblotting, immunofluorescence, live cell imaging and other techniques, we found that GJ whole channels or hemichannels between glia-glia, glia-neurons showed in diverse cellular specific subtypes, distribution, phosphorylation, and thus modulated induction, development and maintenance of mirror image pain. Moreover, the temporal-spatial expression of connexins changed distinctly rat spinal cord and dorsal root ganglion（DRG）, and was asymmetrical at both sides to noxious stimuli. Furthermore, diverse phosphorylational sites of connexins such as Cx43, by different protein kinases including PKA, PKC, MAPK and src, were relative to gating, transcription, translation and posttranslational trafficking of GJs, by which to meet synaptic transmission in spinal and DRG control of mirror image pain. These results indicate that differential temporalspatial expression and dynamic phosphorylation of connexins, especially Cx43, if any more, is one of indispensable peripheral and central modulation to induction and spreading of mirror image pain.

关键词： Gap junctions connexins Mirror image pain Phosphorylation

Dorsal root ganglion and spinal dopamine D2 receptor-Cx43signaling pathways regulating mirror image pain induced by scorpion sting

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Dorsal root ganglion and spinal dopamine D2 receptor-Cx43sig...

第12届生物毒素研究及医药应用学术大会

作者： Xia Liu Lei Xi Hong-Ni Zhu Xiao-Xia Zhao Yan-Yan Wu Xiang-Xiang Chen Yu-Tian Song Qiu-Hang Ran Qing-Hu Yang Zhi-Hong Sun Zhan-Tao Bai College of Life Sciences & Research Center for Peptide Drugs Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources Shaanxi Provincial Key Lab of Red Dates

Dopamine,a kind of catecholamine neurotransmitter,is indispensable to pain *** evidences demonstrated that dopamine D2 receptor（DRD2）,gap junction and glia may participate in regulation of pain in different molecular and cellular ***,whether promising interaction between these pain targets existed or not,remains need to be *** we showed that DRD2 blocker and gap junction inhibitor synergistically inhibited rat spontaneous pain behaviors,bilateral mechanical hypersensitivity and unilateral thermal *** cell imaging demonstrated that the gap junctional hemi-channels of cultured astrocytes could be opened by Dopamine,and Dopamine-induced opening were reduced by DRD2 ***,suppression of DRD2 significantly decreased the bilateral co-expression of Cx43 and GFAP protein in spinal cord and dorsal root *** results support the points that glia DRD2-Cx43 intracellular signaling pathways may directly mediate pain spreading from the injured side to contralateral side by asymmetric temporal differences,thus providing a novel understand to pain control and therapy by combined interference of membrane receptor-ion channels.

关键词： Dopamine D2 receptor connexins Mirror image pain

D2-Cx43 signaling pathways regulating mirror image pain

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D2-Cx43 signaling pathways regulating mirror image pain

中国神经科学学会第十二届全国学术会议

作者： Cheng-Hui Cao Sui-Bin Ma Qing-Hu Yang Jia Li Yan-Yan Wu Xiang-Xiang Chen Lei Xi Huan Guo Dan-Yang Li Qi Wang Ruo-Song Ai Gao Rui Xu-Ri Zhang Xia Liu Zhan-Tao Bai College of Life Sciences Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources

Dopamine, a kind of catecholamine neurotransmitter, is indispensable to pain responses. Multiple evidences demonstrated that dopamine D2 receptor（DRD2）, gap junction and glia may participate in regulation of pain in different molecular and cellular pathways. However, whether promising interaction between these pain targets existed or not, remains need to be elucidated. Here we showed that DRD2 blocker and gap junction inhibitor synergistically inhibited rat spontaneous pain behaviors, bilateral mechanical hypersensitivity and unilateral thermal hypersensitivity. Live cell imaging demonstrated that the gap junctional hemi-channels of cultured astrocytes and microglia could be opened by Dopamine, and Dopamine-induced opening were reduced by DRD2 blocker. Furthermore, suppression of DRD2 significantly decreased the bilateral co-expression of Cx43 and GFAP protein in spinal cord and dorsal root ganglion. These results support the points that glia DRD2-Cx43 intracellular signaling pathways may directly mediate pain spreading from the injured side to contralateral side by asymmetric temporal differences, thus providing a novel understand to pain control and therapy by combined interference of membrane receptor-ion channels.

关键词： Dopamine D2 receptor connexins Mirror image pain

Novel alpha2A adrenergic receptor-Cx43 cellular signaling pathway mediating mirror image pain induced by scorpion sting

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Novel alpha2A adrenergic receptor-Cx43 cellular signaling pa...

第12届生物毒素研究及医药应用学术大会

作者： Xiao-Xia Zhao Yan-Yan Wu Xiang-Xiang Chen Hong-Ni Zhu Cheng-Hui Cao Lei Xi Ren-Hao Hou Qing-Hu Yang Yan-Heng Zhou Zhi-Hong Sun Xia Liu Zhan-Tao Bai College of Life Sciences & Research Center for Peptide Drugs Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources Shaanxi Provincial Key Lab of Red Dates

Alpha2-adrenergic receptor（alpha2-AR） is involved in the modulation of pain occurrence and *** reported that alpha2A-AR controlled the conduction and permeability of gap junction channels in heart muscle and cancer ***,whether functional interaction between alpha2A-AR and gap junction channels worked or not,is for from *** found that alpha2-AR agonist and gap junction blocker synergistically inhibited BmK I（scorpion Buthus martensii Karsch）-induced mirror image pain *** co-localization and qualitative assays revealed that the co-expression of alpha2A-AR and Cx43 was mainly distributed in *** addition,live cell imaging verified that neurotransmitter noradrenaline activated and opened astrocyte gap junctional ***,the noradrenaline-drived dye movement was blocked evidently by alpha2-AR agonist or gap junction blocker individually,and by them *** study indicates that the novel alpha2A-AR-Cx43 signaling pathways may mediate the induction,development,maintenance and recovery of mirror image *** findings would help to elucidate the persistence,chronicalization,diversities,personalization of pain mechanisms,and further provide some effective anti-pain strategies combing alpha2A-AR and connexin drugs.

关键词： Noradrenaline Alpha2-adrenergic receptor connexins Mirror image pain

5-HT2A receptor-Cx43 signaling pathway participating in mirror image pain induced by scorpion sting

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5-HT2A receptor-Cx43 signaling pathway participating in mirr...

第12届生物毒素研究及医药应用学术大会

作者： Zhi-Hong Sun Hong-Ni Zhu Xiao-Xia Zhao Yu-Ying Han Cheng-Hui Cao Jiang-Bo Wang Qing-Hu Yang Yan-Heng Zhou Xia Liu Zhan-Tao Bai College of Life Sciences & Research Center for Peptide Drugs Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources Shaanxi Provincial Key Lab of Red Dates

Serotonin(5-HT),a neuroactive substances,play an important role in the descending inhibitory and descending facilitation system.5-HT receptors,especially 5HT receptor,showed dual-directional regulation of nociceptive information,and modulated chronic *** addition,many evidences demonstrated that the 5-HT receptor(5-HT),gap junction intercellular communication,glia may participate in the regulation of pain through different molecular and cellular ***,whether their interactions are underlying or not,remains to be a necessary *** found that 5-HT antagonist significantly suppressed BmK(scorpion Buthus martensii Karsch) I-induced spontaneous pain,bilateral mechanical hypersensitivity and unilateral thermal *** pain condition,the expression of 5-HT receptor,connexin 43 and glia,showed an obvious asymmetry and variation in spinal cord and dorsal root *** addition,5-HT receptor was co-localized differentially with neuronal and glia markers and connexin ***,the gap junction hemi-channels in cultured astrocyte were opened by 5-HT,and the opening were reduced by5-HT *** indicates that the 5-HT-Cx43 signaling pathways at least in part,modulate the induction,development,maintenance and recovery of mirror image *** findings would help to elucidate the persistence,chronicalization,diversities,personalization of pain mechanisms,and further provide an effective analgesia strategy combing with 5-HTand connexins.

关键词： Serotonin 5-HT2Areceptor connexins Mirror image pain