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IL-33及其ST2受体在神经系统中的表达及其介入疼痛相关疾病的研究进展

中国医师杂志 2016年第4期18卷 512-515页

作者：周搏罗剑刚鄢建勤中南大学湘雅医院麻醉科长沙410008

白介素-33（IL-33）是多功能细胞因子,属于IL-1家族.IL-33既可以发挥转录抑制因子作用,也可以与受体生长刺激表达基因2蛋白（ST2）结合,在免疫调节及炎症进程中扮演着重要的角色.近来研究表明IL-33在神经系统中广泛分布,在疼痛相关疾病... 详细信息

白介素-33（IL-33）是多功能细胞因子,属于IL-1家族.IL-33既可以发挥转录抑制因子作用,也可以与受体生长刺激表达基因2蛋白（ST2）结合,在免疫调节及炎症进程中扮演着重要的角色.近来研究表明IL-33在神经系统中广泛分布,在疼痛相关疾病的发生发展中,IL-33及其受体ST2发挥着重要的作用.本文就IL-33/ST2的生物学特点及其在神经系统表达和介入疼痛相关疾病的意义进行综述.

关键词：白细胞介素1/代谢受体,白细胞介素1/代谢神经系统/代谢疼痛/代谢综述

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Cloning and characterization of a Na⁺-driven anion exchanger (NDAE1) -: A new bicarbonate transporter

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JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第32期275卷 24552-24559页

作者： Romero, MF Henry, D Nelson, S Harte, PJ Dillon, AK Sciortino, CM Case Western Reserve Univ Sch Med Dept Physiol & Biophys Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Pharmacol Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Genet Cleveland OH 44106 USA

Regulation of intra- and extracellular ion activities (e,g. H+, Cl-, Na+) is key to normal function of the central nervous system, digestive tract, respiratory tract, and urinary system. With our cloning of an electrogenic Na+/HCO3- cotransporter (NBC), we found that NBC and the anion exchangers form a bicarbonate transporter superfamily, Functionally three other HCO3- transporters are known: a neutral Na+/HCO3- cotransporter, a K+/HCO3- cotransporter, and a Na+-dependent Cl--HCO3- exchanger. We report the cloning and characterization of a Na+-coupled Cl--HCO3- exchanger and a physiologically unique bicarbonate transporter superfamily member. This Drosophila cDNA encodes a 1030-amino acid membrane protein with both sequence homology and predicted topology similar to the anion exchangers and NBCs, The mRNA is expressed throughout Drosophila development and is prominent in the central nervous system. When expressed in Xenopus oocytes, this membrane protein mediates the transport of Cl-, Na+, H+, and HCO3- but does not require HCO3-. Transport is blocked by the stilbene 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonates and may not be strictly electroneutral. Our functional data suggest this Na+ driven anion exchanger (NDAE1) is responsible for the Nai-dependent Cl--HCO3- exchange activity characterized in neurons, kidney, and fibroblasts. NDAE1 may be generally important for fly development, because disruption of this gene is apparently lethal to the Drosophila larva.

关键词： 4 4'-二异硫氰基苯-2 2'-二磺酸/药理学氨基酸序列反向转运物/化学反向转运物/遗传学反向转运物/生理学碳酸氢盐类/代谢氯化重碳酸反向转运物氯化物/代谢染色体图克隆分子 DNA 互补果蝇属/遗传学果蝇属/生理学胚胎非哺乳动物氢离子浓度膜电位/药物作用模型分子分子序列数据神经系统/代谢卵母细胞/生理学种系发生蛋白质结构二级重组蛋白质类/化学重组蛋白质类/代谢序列比对序列同源性氨基酸钠/代谢转录遗传爪蟾光滑动物女(雌)性

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Development of neuron-neuron synapses

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CURRENT OPINION IN NEUROBIOLOGY 2000年第1期10卷 125-131页

作者： Lee, SH Sheng, M Massachusetts Gen Hosp Dept Neurobiol Boston MA 02114 USA Massachusetts Gen Hosp Howard Hughes Med Inst Boston MA 02114 USA Harvard Univ Sch Med Boston MA 02114 USA

Our understanding of neuronal synapse development has advanced in recent years. The development of glycinergic synapses appears to depend on gephyrin and glycine receptor activity. Molecular characterization of the structure and development of glutamatergic synapses is in progress, but the underlying mechanisms remain unclear. Activity-dependent mechanisms and specific molecules that regulate the morphological development of dendritic spines have recently been identified.

关键词：树突/代谢运动神经肌肉终板/化学运动神经肌肉终板/代谢神经生长因子类/生理学神经生长因子类/分泌神经组织蛋白质类/代谢神经系统/细胞学神经系统/生长和发育神经系统/代谢神经元/细胞学神经元/代谢受体谷氨酸/代谢突触/化学突触/代谢突触/生理学动物人类

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JNK and p38 stresskinases - degenerative effectors of signal-transduction-cascades in the nervous system

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PROGRESS IN NEUROBIOLOGY 2000年第1期61卷 45-60页

作者： Mielke, K Herdegen, T Univ Kiel Dept Pharmacol D-24105 Kiel Germany

The c-Jun N-terminal kinases (JNKs, also called stress activated protein kinases, sAPKs) and p38 kinases constitute together with extracellular signal-regulated kinases (ERKs) the family of MAP kinases. Whereas the functions of JNKs under physiological conditions are largely unknown, there is raising evidence that JNKs are potent effecters of apoptosis or degeneration of neurons in vitro and in the brain. The activation of the inducible transcription factor c-Jun by N-terminal phosphorylation is a central event in JNK-mediated degenerative processes that depend on de novo protein synthesis. At the post-translational level, cytoplasmic degenerative actions of JNKs might comprise inhibition of Bcl-2 and steroid hormone-receptor signaling or hyperphosphorylation of tan, and at transcriptional level, JNKs might trigger the induction of the apoptotic effectors p53 and Fas-Ligand by phosphorylation of c-Jun. The role of p38 is the nervous system is poorly understood, but its activation is also considered as part of the neuronal stress response. This review informs about the genetic processing, the regulation of activity and the biochemical actions of JNK and p38 isoforms in general. In the second part, we summarize the findings on expression and activation of JNKs and p38 under neurodegenerative condition. A particular focus is also put on the putative function of JNK under physiological conditions and for neuroprotection. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：细胞凋亡/生理学丝裂原活化蛋白激酶8 丝裂原激活蛋白激酶类/代谢丝裂原激活蛋白激酶类/生理学神经系统/代谢神经系统生理学信号传导/生理学 p38丝裂原活化蛋白激酶类动物人类

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Semaphorins and their receptors in vertebrates and invertebrates

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CURRENT OPINION IN NEUROBIOLOGY 2000年第1期10卷 88-94页

作者： Raper, JA Univ Penn Sch Med Philadelphia PA 19104 USA

The semaphorins are a family of intercellular signaling proteins that has grown to include 19 identified members in higher vertebrates. Several of its members act as axonal guidance molecules. One participates in signaling in the immune system. The majority, however, do not yet have known biological functions. Recent studies have shown that neuropilins and plexins act as receptors for semaphorins. The most important challenge for the future is to define the biological roles of semaphorins in vivo.

关键词：轴突/代谢细胞运动基因缺失糖蛋白类/遗传学糖蛋白类/代谢无脊椎动物神经组织蛋白质类/遗传学神经组织蛋白质类/代谢神经系统/细胞学神经系统/胚胎学神经系统/生长和发育神经系统/代谢神经纤毛蛋白质1 信号素3A 信号传导脊椎动物动物小鼠

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Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第22期97卷 12044-12049页

作者： Incardona, JP Lee, JH Robertson, CP Enga, K Kapur, RP Roelink, H Univ Washington Dept Biol Struct Seattle WA 98195 USA Univ Washington Ctr Dev Biol Seattle WA 98195 USA Univ Washington Dept Pathol Seattle WA 98195 USA

Patched (Ptc) is the ligand-binding component of the Hedgehog (Hh) receptor complex. In the Drosophila embryo, Ptc and Hh colocalize in vesicular punctate structures. However, receptor-mediated endocytosis of Hh proteins has not been demonstrated. By using chick neural plate explants, we show that Sonic hedgehog (Shh)-responsive neural precursor cells internalize recombinant and endogenous Shh and provide direct evidence for a gradient of endogenous Shh in the ventral neural tube. Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc-binding site of Shh. These findings suggest that Shh internalization is mediated by Ptc-l and may be linked to signaling. Concordantly, transfection of mammalian cell lines with a Ptc-l cDNA confers the ability to internalize multiple forms of Shh, including transmembrane-anchored Shh, by a dynamin-dependent process.

关键词：细胞系果蝇蛋白质类动力蛋白质类胞吞作用 GTP磷酸水解酶类/代谢猬蛋白质类昆虫蛋白质类/代谢膜蛋白质类/代谢神经系统/细胞学神经系统/胚胎学神经系统/代谢蛋白质类/代谢受体细胞表面/代谢信号传导反式激活因子类动物人类

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The role of 6R-tetrahydrobiopterin in the nervous system

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PROGRESS IN NEUROBIOLOGY 2000年第4期61卷 415-438页

作者： Koshimura, K Murakami, Y Tanaka, J Kato, Y Shimane Med Univ Dept Med Div 1 Izumo Shimane 6938501 Japan

In addition to its cofactor activities for aromatic L-amino acid hydroxylases and nitric oxide synthase (NOS), 6R-tetrahydrobiopterin (6R-BH4) shows diverse actions on neurons. Dopamine release from the rat striatum or PC12 cells was stimulated by 6R-BH4, The action of 6R-BH4 was independent of its cofactor activities and stereospecific. Ca2+ channels in rat brain and PC12 cells were activated by 6R-BH4 via cAMP-protein kinase A pathway. Membrane potential of PC12 cells was deplorized by 6R-BH4. Thus, it is assumed that 6R-BH4 acts on its specific action site (possibly outside of the cell membrane) to stimulate dopamine release by activating Ca2+ channels, Apoptosis induced by depletion of serum and nerve growth factor in PC12 cells was prevented by 6R-BH4. The cell surviving effect of 6R-BH4 was also mediated by activation of Ca2+ channels and cAMP-protein kinase A pathway. However, since 6R-BH4 did not activate mitogen activated protein kinase, it did not support neuronal differentiation, Nitric oxide (NO)-induced cell death was prevented by 6R-BH4 in PC12 cells. NOS activity was not changed by exogenous 6R-BH4, but NO metabolites in culture medium were decreased by 6R-BH4. When endogenous 6R-BH4 was reduced by inhibition of biosynthesis, cell death was induced in PC12 cells. Superoxide is observed to be generated during autoxidation of 6R-BH4. Superoxide producing system mimicked the cell protective action of 6R-BH4 against NO toxicity. Thus, it is considered that 6R-BH4 protects PC12 cells against NO toxicity by generating superoxide during its autoxidation. These results raised the possibility that 6R-BH4 is a self-protective factor against NO toxicity in NO producing neurons, Our findings indicate that 6R-BH4 regulates neuronal activities in the brain and that 6R-BH4 can be a promising drug for neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. (C) 2000 Elsevier Science Ltd, All rights reserved.

关键词：生物蝶呤/类似物和衍生物生物蝶呤/代谢生物蝶呤/药理学钙通道/药物作用钙通道/代谢细胞存活/药物作用多巴胺/代谢神经系统/细胞学神经系统/药物作用神经系统/代谢一氧化氮/代谢一氧化氮/毒性 PC12细胞动物大鼠

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Postsynaptic filopodia in muscle cells interact with innervating motoneuron axons

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NATURE NEUROSCIENCE 2000年第10期3卷 1012-1017页

作者： Ritzenthaler, S Suzuki, E Chiba, A Univ Illinois Dept Cell & Struct Biol Urbana IL 61801 USA Univ Illinois Program Neurosci Urbana IL 61801 USA Univ Tokyo Inst Med Sci Dept Fine Morphol Tokyo 1088639 Japan

Precise synaptogenesis is crucial to brain development, and depends on the ability of specific partner cells to locate and communicate with one another. Dynamic properties of axonal filopodia during synaptic targeting are well documented, but the cytomorphological dynamics of postsynaptic cells have received less attention. In Drosophila embryos, muscle cells bear numerous postsynaptic filopodia ('myopodia') during motoneuron targeting. Here we show that myopodia are actin-filled microprocesses, which progressively clustered at the site of motoneuron innervation while intermingling with presynaptic filopodia. In prospero mutants, which have severe delays in axon outgrowth from the CNS, myopodia were present initially but clustering behavior was not observed, demonstrating that clustering depends on innervating axons. Thus, postsynaptic filopodia are capable of intimate interaction with innervating presynaptic axons. We propose that, by contributing to direct long-distance cellular communication, they are dynamically involved in synaptic matchmaking.

关键词：肌动蛋白类/药物作用肌动蛋白类/代谢躯体发育模式/生理学细胞间通讯/生理学果蝇黑腹绿色荧光蛋白质类生长锥/代谢生长锥/超微结构指示剂和试剂发光蛋白质类运动神经元/代谢运动神经元/超微结构肌骨骼/胚胎学肌骨骼/代谢肌骨骼/超微结构神经系统/胚胎学神经系统/代谢神经系统/超微结构神经肌肉接头/胚胎学神经肌肉接头/代谢神经肌肉接头/超微结构伪足/代谢伪足/超微结构突触膜/代谢突触膜/超微结构时间因素动物

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Molecular insights into mRNA transport and local translation in the mammalian nervous system

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NEURON 2000年第1期25卷 19-28页

作者： Kiebler, MA DesGroseillers, L Max Planck Inst Entwicklungsbiol D-72076 Tubingen Germany Univ Montreal Dept Biochem Montreal PQ H3C 3J7 Canada

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Kurtz, a novel nonvisual arrestin, is an essential neural gene in Drosophila

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GENETICS 2000年第3期155卷 1281-1295页

作者： Roman, G He, J Davis, RL Baylor Coll Med Dept Mol & Cellular Biol Houston TX 77030 USA

The kurtz gene encodes a novel nonvisual arrestin, krz is located at the most-distal end of the chromosome 3R, the third gene in from the telomere. krz is expressed throughout development. During early embryogenesis, hit is expressed ubiquitously and later is localized to the central nervous system, maxillary cirri, and antennal sensory organs. In late third instar larvae, krz message is detected in the fat bodies, the ventral portion of the thoracic-abdominal ganglia, the deuterocerebrum, the eye-antennal imaginal disc, and the wing imaginal disc. The krz(1) mutation contains a P-element insertion within the only intron of this gene and results ill a severe reduction of function. Mutations in krz have a broad lethal phase extending from late embryogenesis to the third larval instar. The fat bodies of krz(1) larva precociously dissociate during the midthird instar. krz(1) is a type 1 melanotic tumor gene;the fat body is the primary site of melanotic tumor formation during the third instar. We have functionally rescued these phenotypes with both genomic and cDNA transgenes. Importantly, the expression of a full-length krz cDNA within the CNS rescues the krz(1) lethality. These experiments establish the krz nonvisual arrestin as an essential neural gene in Drosophila.

关键词：动物基因修饰抑制蛋白/遗传学抑制蛋白类果蝇蛋白质类果蝇黑腹/遗传学脂肪体/代谢脂肪体/病理学基因表达基因基因必要/遗传学基因致死/遗传学昆虫蛋白质类/遗传学昆虫蛋白质类/代谢幼虫/代谢黑色素瘤/遗传学黑色素瘤/病理学分子序列数据突变神经系统/胚胎学神经系统/代谢表型物理染色体图序列分析 DNA 序列同源性氨基酸转录遗传转染动物女(雌)性男(雄)性

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