SPX

更新于：2025-05-07

基本信息

别名

C12orf39、MGC10946、Neuropeptide Q

+ [7]

简介

Plays a role as a central modulator of cardiovascular and renal function and nociception. Also plays a role in energy metabolism and storage. Inhibits adrenocortical cell proliferation with minor stimulation on corticosteroid release (By similarity). Acts as a ligand for galanin receptors GALR2 and GALR3 (PubMed:17284679, PubMed:24517231). Intracerebroventricular administration of the peptide induces an increase in arterial blood pressure, a decrease in both heart rate and renal excretion and delayed natriuresis. Intraventricular administration of the peptide induces antinociceptive activity. Also induces contraction of muscarinic-like stomach smooth muscles. Intraperitoneal administration of the peptide induces a reduction in food consumption and body weight. Inhibits long chain fatty acid uptake into adipocytes (By similarity). Intracerebroventricular administration of the peptide induces a decrease in heart rate, but no change in arterial pressure, and an increase in urine flow rate. Intraventricular administration of the peptide induces antinociceptive activity (By similarity).

关联

项与 SPX 相关的药物

CN117883548

专利挖掘

靶点

SPX

作用机制-

在研机构

哈尔滨医科大学附属第一医院（哈尔滨医科大学第一临床医学院、黑龙江省血液肿瘤研究所、黑龙江省干细胞库、黑龙江省肝脾外科中心）

原研机构

哈尔滨医科大学附属第一医院（哈尔滨医科大学第一临床医学院、黑龙江省血液肿瘤研究所、黑龙江省干细胞库、黑龙江省肝脾外科中心）

在研适应症

心脏病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SPX 相关的临床结果

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100 项与 SPX 相关的转化医学

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0 项与 SPX 相关的专利（医药）

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1,100

项与 SPX 相关的文献（医药）

2025-06-01·Peptides

Spexin expression in the human bile duct and perihilar cholangiocarcinoma

Article

作者: Feichtinger, René G ; Kraus, Theo ; Varga, Martin ; Hochmann, Sarah ; Kofler, Barbara ; Sotlar, Karl ; Gaisbauer, Stefanie ; Huber, Sara ; Fitzner, Theresia

The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL_1-3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL₂-R and GAL₃-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (p = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.

2025-05-01·Plant Physiology and Biochemistry

High relative humidity mitigates the adverse effects of excessive light by protecting photosynthetic machinery in flowering Chinese cabbage

Article

作者: Wang, Tingqin ; Pan, Gengzhen ; Kang, Yunyan ; Yang, Xian ; Chai, Xirong ; Zhang, Jintao ; Zhong, Min

Increasing canopy relative air humidity (RH) facilitates the resistance of flowering Chinese cabbage plants against excessive light exposure in a plant factory with artificial lighting (PFAL), thereby completely inhibiting leaf burn occurrence. To clarify this high RH-mediated resistance mechanism, we further analyzed the transcriptomes, gas exchange parameters, and chlorophyll fluorescence of flowering Chinese cabbage plants subjected to two levels of canopy RH (70% and 90%). Transcriptomic data revealed a significant enrichment of photosynthesis antenna proteins pathway, which was notably downregulated in both the cotyledons and the first true leaves of the plants grown at 70% RH from the 10th to the 14th day after sowing. However, the downregulation of the photosynthesis-antenna proteins pathway in the first true leaves was notably attenuated by increasing the RH from 70% to 90%, consequently inhibiting the down-regulated expression of all light-harvesting complex I- and II-subunit-encoding mRNAs. The 70% RH-treated seedlings exhibited serious photoinhibition, as indicated by relatively lower non-photochemical quenching (NPQ), maximal quantum yield of photosystem I and II, and adaptation of the photosynthetic apparatus to high irradiance. The 90% RH treatment greatly lessened the reduction of NPQ and relative electron transport rates, which favored dissipating the excess excited energy, protected the photosynthetic apparatus against photodamage, and ultimately completely inhibited leaf burn occurrence. Overall, our results indicate that high canopy RH could improve the resistance of plants to intense light by maintaining efficient photosynthesis, thereby minimizing reliance on supplemental artificial lighting.

2025-05-01·Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Antarctic lichens exhibit diverse photobiont distributions and a complex regulation of non-photochemical quenching

Article

作者: Vítek, Petr ; Mishra, Kumud Bandhu ; Mishra, Anamika ; Barták, Miloš

The structure, function, and molecular mechanisms of lichen survival in harsh habitats like Antarctica and Alpine localities, where environmental extremes change frequently, are highly interesting yet largely underexplored. We used high resolution microscopy, Raman spectroscopy, and chlorophyll a fluorescence to investigate the basic structure and function, i.e., intrathalline distribution and allocation of photobionts, as well as the heat dissipation process in three Antarctic lichens: Dermatocarpon polyphyllizum (DP), Umbilicaria antarctica (UA), and Leptogium puberulum (LP). Microscopic images of their transverse slices revealed visual insights into the heterogeneous distribution of photobionts within their structurally distinct thalli. Raman spectra showed shifts in the carotenoid Raman ν₁(CC) band between lichens with algal (DP and UA) and cyanobacterial (LP) photobionts, and interestingly, they revealed biosynthesis of scytonemin, a UV-screening pigment, in cyanolichen LP. We found that increasing actinic irradiance has a nearly equal effect on the shape of chlorophyll fluorescence transients also during dark relaxation in lichens with algal photobionts, but it differed greatly for cyanolichen LP. The dark relaxation kinetics of non-photochemical quenching (NPQ) in experimental lichens differed significantly between lichens with algal photobionts DP and UA; however, this parameter could not be calculated in cyanolichen LP. The components of NPQ revealed that rapidly relaxing energy dependent quenching, Φ_qE, is active and protects the thallus of DP predominantly; however, in UA state transition quenching, Φ_qT, predominates. The diversity in NPQ across the three examined lichens revealed intriguing aspects of heat dissipation in their photobionts as a mechanism for survival under Antarctica conditions.

项与 SPX 相关的新闻（医药）

2024-08-22

·生物探索

Nature | 姜道华团队揭示磷酸转运蛋白XPR1转运和调控的分子机制

引言无机磷酸盐（Pi）是所有生命体必需的常量营养元素，几乎参与所有的生物过程，在物质合成、呼吸作用、光合作用、能量转换、信号传导等生理过程中发挥不可或缺的作用。生物体内磷酸盐水平受到严格调控，磷酸盐的缺失或过量会对生物体造成重大疾病，包括心功能障碍，佝偻病，骨软化症及血管钙化等。XPR1是目前人体中唯一已知的磷酸盐外排转运蛋白，其功能异常会导致人类神经系统疾病原发性家族性脑钙化和肾范可尼综合征。XPR1包含一个可溶的SPX结构域和一个跨膜结构域，其中SPX结构域是一个保守的多磷酸肌醇（InsPP）传感器， SPX结构域通过监控细胞内InsPP的浓度，调控转运蛋白外排磷酸盐的活性。然而，XPR1外排磷酸根以及其活性被SPX结构域调控的分子机制仍然未知。中国科学院物理研究所/北京凝聚态物理国家研究中心软物质与生物物理实验室SM10组姜道华特聘研究员长期从事于物质跨膜运输的研究，近年来在离子通道蛋白[Cell, 184 (2021); NSMB 29, (2022); Nat. Commun. 1030, (2023); Nat. Commun. 1286, (2022); Nat. Commun. 1286, (2713); Nat. Chem. Biol. 19, (2023); Cell Reports 42, (2023); Cell Reports 37, (2021)]和转运蛋白[Nature 626, (2024); Cell Research 34, (2024); NSMB 31, (2024)]介导的物质跨膜运输方面取得进展。 2024年8月 21日，姜道华特聘研究员团队在Nature上发表了文章Human XPR1 structures reveal phosphate export mechanism，通过冷冻电镜单颗粒技术重构出磷酸盐转运蛋白XPR1处于不同构象的高分辨率结构，首次揭示了XPR1外排磷酸根离子的门控机制和SPX结构域的调控机制。在这项研究中，作者解析了XPR1结构处于关闭，开放和结合肌醇-6磷酸的三种不同构象，首次发现XPR1二聚体形式。基于结构和功能结果，作者提出了XPR1门控机制和SPX结构域的调控机制模型。XPR1门控机制主要由TM9b的构象变化介导，磷酸根被靠近细胞内侧的位点一和位于细胞膜中间的位点二识别和结合，通过与W573相互作用，进而引发TM9b构象变化，使XPR1处于打开状态（图一）。而SPX结构域可以通过感受细胞内磷酸肌醇的浓度来调控XPR1外排磷酸根离子的通量：当细胞内磷酸根浓度较低时，多磷酸肌醇浓度降低，SPX结构域呈动态构象，XPR1的C-loop结合在位点一附近并降低限制磷酸根进入蛋白磷酸根入口；当细胞内磷酸根浓度升高时，多磷酸肌醇浓度升高，SPX结构域结合多磷酸肌醇并转换为稳定构象，稳定状态的SPX结构域与C-loop相互作用，使其远离磷酸根入口，从而加速Pi的外排（图二）。由于磷酸根结合位点，TM9和C-loop，以及SPX结构域在酵母SYG1，植物PHO1和其他动物中的XPR1中高度保守，因此，作者推测这些蛋白应该采用类似的机制来维持Pi的稳态。图一 XPR1不用构象的结构(Credit: Nature) 图二 XPR1磷酸盐转运调节机制模型(Credit: Nature) 该研究发现了XPR1的结构类似于转运蛋白，但是采取一种新颖的类似于通道的门控机制外排磷酸根，显著不同于绝大多数转运蛋白采用的交替开放的转运机制。此外，该研究首次阐明了SPX结构域通过结合多磷酸肌醇调节XPR1的通量，提出多磷酸肌醇感知和磷酸跟输出之间的耦合机制，这些对人体磷酸根稳态的研究至关重要。参考文献 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-024-07852-9 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

2024-05-14

·生物探索

Circulation | 哈尔滨医科大学潘振伟/杨宝峰/张志仁/李悦发现心房颤动的潜在治疗新靶点

引言G蛋白偶联受体在心房颤动(AF)中起关键作用。Spexin是一种新型的丙氨酸受体( GALRs)配体。2024年5月10日，哈尔滨医科大学潘振伟、杨宝峰、张志仁及李悦共同通讯在Circulation（IF=38）在线发表题为“Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2”的研究论文，该研究证明，Spexin通过作用于丙氨酸受体2减少心房颤动易感性。该研究表明，房颤患者的Spexin血浆水平低于非房颤患者，敲除Spexin会增加小鼠的房颤易感性。SPX-KO小鼠心房钾内整流通道亚家族J成员2 (KCNJ2)和肌磷脂(SLN)上调；同时，SPX-KO小鼠离体心房肌细胞I K1电流升高，Ca2+处理受损。GALR2-cKO小鼠，而不是GALR1-cKO和GALR3-cKO小鼠，具有更高的AF发生率，这与更高的IK1电流和细胞内Ca2+过载有关。SPX-KO和GALR2-cKO小鼠心房组织中环AMP反应元件结合蛋白1 (CREB)磷酸化水平上调。染色质免疫沉淀证实了p-CREB在KCNJ2和SLN的近端启动子区域的募集。最后，spexin处理抑制CREB信号，降低IK1电流和细胞内Ca2+过载，从而降低了 Ang-II注入小鼠AF的诱导性。总之，Spexin通过抑制CREB磷酸化，从而下调GALR2受体对KCNJ2和SLN的转录，从而降低房颤易感性。spexin/GALR2/CREB信号通路为房颤药物的开发提供了一条新的治疗途径。房颤(AF)是最常见的心律失常，具有相当高的发病率和死亡率，其治疗伴有不良的心房重构。目前治疗房颤的药理学策略疗效有限，且存在一定的不良反应。发现与房颤病理生理机制相关的新靶点可能会开辟新的治疗途径。房颤的进展是心房电和结构重构、自主神经失衡、Ca2+处理改变、代谢异常和遗传因素的结果。电重构导致心房有效不应期(AERP)和动作电位持续时间(APD)缩短，并导致APD适应性的丧失，这涉及到伴随的离子活性改变慢性房颤患者的离子通道重塑包括L型Ca2+电流(ICa, L)密度降低，向内整流K+电流(I K1)振幅增加和细胞内Ca2+处理紊乱。心脏SERCA2a(肌浆网Ca2+-ATP酶2a)参与Ca2+进入肌浆网的再摄取，并关键地决定了肌浆网(CaSR)中的钙含量和心脏的兴奋-收缩偶联。PLN(磷蛋白)和SLN(肌磷脂)是心脏SERCA泵活性的关键调节因子。细胞内Ca2+处理的变化降低了心房肌细胞的收缩功能，缩短了心房肌细胞的动作电位，诱发房颤。心房IK1密度的增加和细胞内Ca2+处理的紊乱在APD缩短和房颤的发生中起着关键作用。抑制心房IK1电流和恢复细胞内Ca2+处理具有开发房颤新药的潜力。模式图（Credit: Circulation）Spexin，也被称为神经肽Q，是最近发现的一种由14个氨基酸组成的肽激素。它广泛产生于大脑，包括下丘脑，以及周围组织，如胃肠道、肺、胰腺、肾脏、肾上腺和脂肪组织。Spexin也被分泌到血液可以改变器官和组织的生理功能。研究表明，肥胖儿童的spexin循环水平低于体重正常的同龄人此外，spexin是运动改善肥胖诱导的胰岛素抵抗和2型糖尿病的潜在介质。它涉及体内平衡功能，如代谢、能量稳态和生殖等。为了发挥这些作用，spexin结合到膜甘丙肽受体2 (GALR2)和甘丙肽受体3 (GALR3)，但不结合到甘丙肽受体1 (GALR1)。在之前的研究中，spexin可以保护心肌细胞免受缺氧诱导的代谢和线粒体功能障碍。该研究系统检测了spexin对AF易感性的影响及其分子机制。研究证明spexin通过GALR2/CREB(环AMP响应元件结合蛋白1)途径抑制Kir2.1和SLN的表达，从而减轻AF的易感性。Spexin/GALR2/CREB信号轴通过调控KCNJ2和SLN转录影响心房电重构和细胞内钙稳态，从而参与房颤的发病。Spexin治疗可抑制心房颤动的易感性，可能是一种治疗心房颤动的新药物。原文链接https://doi-org.libproxy1.nus.edu.sg/10.1161/CIRCULATIONAHA.123.067517责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

临床结果