更新于：2024-09-05

SRD5A3

更新于：2024-09-05

基本信息

别名

3-oxo-5-alpha-steroid 4-dehydrogenase 3、FLJ13352、Polyprenol reductase

+ [8]

简介

Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol (PubMed:20637498). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498). Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism (PubMed:20637498). Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT) (PubMed:17986282, PubMed:26855069).

关联

100 项与 SRD5A3 相关的临床结果

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100 项与 SRD5A3 相关的转化医学

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0 项与 SRD5A3 相关的专利（医药）

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208

项与 SRD5A3 相关的文献（医药）

2023-12-28·Molecules (Basel, Switzerland)

Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite.

Article

作者: Flavia M Zimbres ; Emilio F Merino ; Grant J Butschek ; Joshua H Butler ; Frédéric Ducongé ; Maria B Cassera

Dolichols are isoprenoid end-products of the mevalonate and 2C-methyl-D-erythritol-4-phosphate pathways. The synthesis of dolichols is initiated with the addition of several molecules of isopentenyl diphosphate to farnesyl diphosphate. This reaction is catalyzed by a cis-prenyltransferase and leads to the formation of polyprenyl diphosphate. Subsequent steps involve the dephosphorylation and reduction of the α-isoprene unit by a polyprenol reductase, resulting in the generation of dolichol. The size of the dolichol varies, depending on the number of isoprene units incorporated. In eukaryotes, dolichols are synthesized as a mixture of four or more different lengths. Their biosynthesis is predicted to occur in the endoplasmic reticulum, where dolichols play an essential role in protein glycosylation. In this study, we have developed a selection of aptamers targeting dolichols and enhanced their specificity by incorporating fatty acids for negative selection. One aptamer showed high enrichment and specificity for linear polyisoprenoids containing at least one oxygen atom, such as an alcohol or aldehyde, in the α-isoprene unit. The selected aptamer proved to be a valuable tool for the subcellular localization of polyisoprenoids in the malaria parasite. To the best of our knowledge, this is the first time that polyisoprenoids have been localized within a cell using aptamer-based imaging techniques.

2023-12-13·Molecules (Basel, Switzerland)

Achieving Luminescence of Sr₃Ga_1.98In_0.02Ge₄O₁₄:0.03Cr³⁺ via [In³⁺] Substitution [Ga³⁺] and Its Application to NIR pc-LED in Non-Destructive Testing.

Article

作者: Tao Wang ; Bingkai Gao ; Jiehong Li ; Zhijun Wang ; Panlai Li

Cr³⁺-doped Sr₃Ga₂Ge₄O₁₄:0.03Cr³⁺ (SGGO:0.03Cr³⁺) phosphor was synthesized via a high-temperature solid-phase method. Considering the tunable structure of SGGO, Ga³⁺ ions in the matrix were substituted with In³⁺ ions at a certain concentration. The tuned phosphor produced a red-shifted emission spectrum, with its luminescence intensity at 423 K maintained at 63% of that at room temperature; moreover, the internal quantum efficiency increased to 65.60%, and the external quantum efficiency correspondingly increased to 21.94%. On this basis, SGIGO:0.03Cr³⁺ was encapsulated into a pc-LED, which was applied in non-destructive testing (NDT) experiments, successfully realizing the recognition of water and anhydrous ethanol, proving its potential application in the field of NDT.

2023-11-13·Foods (Basel, Switzerland)

Hair Growth Promotion and Anti-Hair Loss Effects of By-Products Arabica Coffee Pulp Extracts Using Supercritical Fluid Extraction.

Article

作者: Anurak Muangsanguan ; Pichchapa Linsaenkart ; Tanakarn Chaitep ; Jiraporn Sangta ; Sarana Rose Sommano ; Korawan Sringarm ; Chaiwat Arjin ; Pornchai Rachtanapun ; Kittisak Jantanasakulwong ; Yuthana Phimolsiripol ; Juan M Castagnini ; Warintorn Ruksiriwanich

Coffee has been a common ingredient in many traditional hair loss remedies, but limited scientific evidence supports its use, particularly in coffee pulp. Androgenetic alopecia (AGA) is caused by androgens, inflammation, and oxidative stress. In the present study, supercritical fluid extraction (SFE) was used under various conditions to obtain six coffee pulp extracts. The SFE-4 extract, using 50% (v/v) ethanol as a co-solvent at conditions of 100 °C and 500 bars for 30 min, exhibited the highest phenolic, flavonoid, and caffeine contents. Additionally, the SFE-4 extract increased the migration and cell proliferation of HFDPCs (human hair follicle dermal papilla cells), which control hair cycle regulation, and had scavenging effects on ABTS and DPPH radicals. Additionally, the SFE-4 extract showed potassium ion channel opener activity in HFDPCs, as well as a stimulation effect on the enzyme matrix metalloproteinase-2 (MMP-2) (28.53 ± 1.08% of control), which may be related to the vascular endothelial growth factor (VEGF) gene upregulation. In human prostate cancer cells (DU-145) and HFDPC cells, the SFE-4 extract significantly decreased the expression of SRD5A1, SRD5A2, and SRD5A3, an essential pathway involved in AGA. Hair growth factor genes in the Wnt/-catenin (CTNNB1) and Sonic Hedgehog (SHH, SMO, and GLI1) pathways could be significantly activated by the SFE-4 extract. These results imply that employing SFE in coffee pulp extraction could help AGA treatment by preventing hair loss and promoting hair growth pathways. This would help small coffee producers gain economic empowerment and ensure the long-term sustainability of agricultural waste utilization.

项与 SRD5A3 相关的新闻（医药）

2022-10-28

·药融云

基于靶点的药物设计：近年来肝癌药物研发领域的热门靶点归纳

肝癌即起源于肝脏的恶性肿瘤，是全球常见的恶性肿瘤之一，居恶性肿瘤发病顺位的第6位，据GLOBOCAN 2020估算，2020年全球肝癌新发病例数为90.6万例，肝癌预后差，居全球常见恶性肿瘤死因第3位，2020年全球肝癌死亡数为83.0万例[1]。肝癌也是我国常见恶性肿瘤之一，2020年肝癌居我国恶性肿瘤发病顺位第5位，全国2020年新发肝癌病例数为40.0万人，占中国癌症新发病例数9%；2020年肝癌居我国恶性肿瘤死亡顺位第2位，全国2020年死亡肝癌病例数为39.1万人，占中国癌症死亡病例数13%[1]。肝癌根据其病理类型可分为肝细胞癌(HCC)、胆管细胞癌以及混合性肝细胞癌和胆管细胞癌，其中HCC是肝癌最常见的病理类型，占全球所有原发性肝癌的75%～85%，在中国，HCC占所有原发性肝癌的93.0%[2]。肝癌易复发和转移，手术治疗效果欠佳，也缺乏有效的治疗药物，临床上迫切需要开发具有高效低毒的新型药物。因而研究与开发肝癌特异性靶点药物在我国更加具有重要的意义。本文对近两年肝癌药物研发的潜力靶点进行了归纳。DDR1盘状结构域受体1（DDR1）在肝细胞癌组织中表达上调，且在TNM肿瘤分期系统中II-IV期的肝细胞癌组织中的表达高于在TNM肿瘤分期系统中I期的肝细胞癌组织中的表达，且DDR1的高表达与预后不良有关。DDR1靶基因参与了肝细胞癌的转移，DDR1与ARF6相互作用，通过募集PSD4激活ARF6，ARF6的激活及其在肿瘤转移中的作用离不开DDR1的激酶活性。PSD4高表达与肝细胞癌预后不良相关，DDR1通过胶原蛋白诱导的DDR1信号介导的PSD4/ARF6信号促进HCC的转移，提示DDR1和ARF6可能作为新的转移性肝癌预后标志物和治疗靶点[3]。SSH3丝切蛋白磷酸酶3（SSH3）在肝癌组织中的表达显著高于邻近肝组织，在体外细胞系中也存在同样的趋势，表明SSH3在肝癌的发生中起着极其重要的作用。同时发现SSH3在肝细胞癌患者中的过表达与病理分期和肿瘤大小呈正相关。肿瘤细胞可以通过过表达FGF改变自身和细胞外基质，而FGF/FGFR通路的激活与肿瘤细胞的增殖和凋亡密切相关。SSH3可通过FGF/FGFR途径诱导肝肿瘤细胞微环境的改变，从而导致肝癌的进一步恶性进展。SSH3下调后，肝癌细胞中FGF/FGFR通路相关基因FGF1、FGFR1和FGFR2的蛋白表达显著降低。SSH3能够加速肝癌的恶性进展，可能成为肝癌治疗的新靶点[4]。CBX6Zheng等发现染色质结合蛋白6（CBX6）在肝癌细胞系中被介导，多功能分析提示，HCC中CBX6表达升高是一个独立的不良预后因素，CBX6在体内外均可使肝癌细胞显著生长。Wang等研究发现CBX6在HCC组织中的表达显著高于旁组织。CBX6过表达的HCC患者的肿瘤生长速度快、侵袭能力强、临床分期高。进一步研究表明，CBX6通过调控转录因子Snail/ZEB1介导的上皮细胞-间充质转化(EMT)机制增强肝癌细胞的侵袭和转移能力。综上，CBX6在肝癌的发生、发展中起重要作用，可作为HCC的新型预后生物标志物和治疗靶点[5]。SRD5A3公开的数据显示，甾体5α-还原酶3（SRD5A3）在肝癌组织中的表达普遍高于非肝癌肝组织和相应的邻近肝组织。较高的SRD5A3水平预示着肝癌患者总体生存率、无进展生存率、无复发生存率和疾病特异性生存率较差，SRD5A3的缺失抑制了肝癌的生长，提示SRD5A3可能是HCC预后的潜在生物标志物和治疗靶点[7]。MTMR14肌小管蛋白相关蛋白14（MTMR14）在肝癌组织中过表达，并与临床分期呈正相关，MTMR14基因敲除促进了细胞凋亡，抑制了细胞迁移。MTMR14基因敲除也能抑制肝癌的体内转移，抑制MTMR14表达导致N-cadherin和E-cadherin下调，并促进caspase12、caspase9和caspase3的激活，抑制MTMR14是通过线粒体途径而非死亡受体途径诱发细胞凋亡。MTMR14有望成为肝癌诊断和治疗靶点[7]。ID1分化抑制因子1（ID1）蛋白在肝细胞癌中表达上调，并与肝细胞癌患者的肿瘤复发和不良生存密切相关。ID1诱导AURKA上调，增加的AURKA表达随后增强了MYC癌基因的转录水平，导致MYC致癌信号通路的扩增，ID1和AURKA的表达水平呈正相关。ID1和AURKA同时过表达的患者无复发生存率和总生存率较低。进一步的机制研究表明，新的AURKA/Myc下游信号通路介导了ID1诱导的肝癌细胞的生长、迁移、侵袭和耐药，这可能促进对肝癌进展的了解，并为改进晚期肝癌的治疗策略提供新的靶点[8]。LPAR6溶血磷脂酸受体6(LPAR6)是一种G蛋白偶联受体，在细胞形态和毛发生长中发挥重要作用。LPAR6在肝癌患者中的过表达会促进肿瘤的生长，并导致较差的生存。HGF可以特异性地抑制HepG2细胞的增殖，LPAR6是HGF调控的一个关键的肝癌下游基因。研究表明，HGF通过MEK/ERK信号通路抑制HepG2细胞生长，LPAR6受NCOA3的转录调控，HGF可能通过阻断NCOA3和LPAR6的表达来抑制肝癌的增殖。LPAR6基因敲除会导致肝癌细胞系的增殖停滞，并且LPAR6过表达的肝癌患者肿瘤组织显示出更高的增殖活性。这些结果表明，LPAR6是HGF的下游靶点，可能成为潜在的治疗药物靶点[9]。PES1pescadillo核糖体生物发生因子1（PES1）在肝细胞癌中起促进肿瘤的作用，PES1蛋白表达与肝癌患者的临床特征和较短的生存期呈正相关，PES1基因敲除在体外抑制了肝癌细胞的增殖，在体内抑制了肿瘤的生长，PES1可能通过调节PI3K/AKT/GSK3β/CyclinD1信号通路中的关键蛋白来调控肝癌的增殖和肿瘤发生。PES1在调节肝细胞癌的增殖和肿瘤发生中具有新的作用，因此可能成为治疗肝癌的潜在靶点[10]。UCK2尿苷-胞苷激酶2（UCK2）是能将尿苷和胞苷磷酸化成一磷酸尿苷（UMP）和一磷酸胞苷（CMP）的嘧啶核苷激酶，是嘧啶核苷酸补救合成途径中的限速酶。最近的研究表明，UCK2在肝细胞癌组织中过表达并且与肝细胞癌的预后不良有关，UCK2促进了肝癌细胞的增殖和转移。UCK2与EGFR相互作用，阻断EGF诱导的EGFR泛素化和降解，从而导致肝癌细胞中EGFR-AKT通路的激活和转移的增强，提示UCK2可能成为治疗肝癌的潜在靶点[11]。TCP1肝癌组织中TCP1表达量显著高于正常肝组织，患者总体生存率显著低于正常组，这说明肝癌中TCP1表达量与预后不良存在一定相关性，TCP1能够与P53相互作用抑制P53的活性从而激活Wnt7b/β-catein信号通路促进肝癌细胞的增殖和迁移，这提示TCP1在肿瘤增殖转移中发挥重要作用，可能是肝癌潜在的治疗靶点[7]。NUPR1与邻近正常组织相比，核蛋白1（NUPR1）在肝细胞癌组织中显著过表达，NUPR1通过直接与相应的启动子区域结合诱导血小板衍生生长因子A（PDGFA）的转录，诱导内皮细胞血管生成，抑制PDGFA信号通路则可以破坏人脐静脉内皮细胞（HUVECs）的血管生成。NUPR1可能是肝癌潜在的治疗靶点[7]。CCT3含TCP1亚基3的伴侣蛋白（CCT3）与Yes相关蛋白（YAP）和转录因子CP2相互作用，CCT3在肝癌中高表达，与总生存率较差相关，抑制CCT3可抑制肝癌细胞的转化，CCT3可能是肝癌潜在的治疗靶点和生物标志物[7]。SPIN1肝细胞癌组织中SPIN1表达阳性，在临床肝细胞癌组织中高表达，且与肝细胞癌的恶性程度呈正相关。SPIN1可以通过增加肝癌细胞内甘油三酯、胆固醇和脂滴来调节异常的脂代谢，从而显著促进肝癌细胞的增殖。机制上，SPIN1上调肝癌细胞中FASN的表达。SPIN1通过与SREBP1c相互作用共同激活FASN启动子中的转录因子SREBP1c。此外，SPIN1在体内外均能促进肝癌的生长，并能增加小鼠肿瘤组织中甘油三酯、胆固醇和脂滴的水平。SPIN1通过SREBP1c触发的FASN信号调节异常的脂代谢，促进肝癌的生长。在治疗方面，SPIN1可能成为肝癌治疗的新靶点[13]。TMOD3原肌球调节蛋白3（TMOD3）在肝癌细胞和组织中的表达升高。在体外实验中，TMOD3基因的敲除抑制了肝癌细胞的增殖、侵袭和迁移，而TMOD3的异位表达促进了肝癌细胞的增殖、侵袭和迁移，TMOD3过表达激活了MAPK/ERK信号通路，并增加了该通路的其他靶点，包括MMP2和MMP9的水平，TMOD3可能通过MAPK/ERK信号通路促进肝癌细胞的生长、侵袭和迁移，可能成为肝癌治疗的新靶点[7]。总结寻找重大疾病的间接或直接治疗靶点，是研发创新药物的根本，近年来，随着对HCC 病理学及分子生物学机制的研究不断深入，小分子靶向抗 HCC 的药物研究取得了实质性的进展，为HCC 全身性治疗的提供了一种有效选择。参考资料及文献[1]CANCER TODAY官网：https://gco.iarc.fr/today/home[2]赫捷, 陈万青, 沈洪兵, 等. 中国人群肝癌筛查指南(2022, 北京)[J]. 临床肝胆病杂志, 2022, 38(8): 1739-1758.[3]Zhang X, Hu Y, Pan Y, et al. DDR1 promotes hepatocellular carcinoma metastasis through recruiting PSD4 to ARF6[J]. Oncogene, 2022, 41(12): 1821-1834.[4]Shi Q S, Zhang Y H, Long J, et al. SSH3 promotes malignant progression of HCC by activating FGF1-mediated FGF/FGFR pathway[J]. European Review for Medical and Pharmacological Sciences, 2020, 24(22): 11561-11568.[5]Wang J, He H, Jiang Q, et al. CBX6 promotes HCC metastasis via transcription factors snail/zeb1-mediated EMT mechanism[J]. OncoTargets and therapy, 2020, 13: 12489.[6]牛荣婷,曾冬云,王静,龙勤琴,吴小勤,龙喜带.(2022).CBX家族蛋白在肝细胞癌中的研究进展.临床与实验病理学杂志(09),1094-1097.[7]江振洲,范书生,刘家岐,俞沁玮,张陆勇.中国药物作用靶点研究新进展（Ⅰ）[J].药学进展,2022,46(06):471-494.[8]Wu M, Zhou Y, Fei C, et al. ID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway[J]. International Journal of Oncology, 2020, 57(3): 845-857.[9]Zheng X, Jia Y, Qiu L, et al. A potential target for liver cancer management, lysophosphatidic acid receptor 6 (LPAR6), is transcriptionally up-regulated by the NCOA3 coactivator[J]. Journal of Biological Chemistry, 2020, 295(6): 1474-1488.[10]Wang J, Sun J, Zhang N, et al. PES1 enhances proliferation and tumorigenesis in hepatocellular carcinoma via the PI3K/AKT pathway[J]. Life Sciences, 2019, 219: 182-189.[11]Cai J, Sun X, Guo H, et al. Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma[J]. Oncogenesis, 2020, 9(12): 1-14.[12]Liu Y, Zhang X, Lin J, et al. CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer[J]. Cell death & disease, 2019, 10(9): 1-15.[13]Zhao M, Bu Y, Feng J, et al. SPIN1 triggers abnormal lipid metabolism and enhances tumor growth in liver cancer[J]. Cancer Letters, 2020, 470: 54-63. —END—联系我们，体验药融云更多专业服务会议合作园区服务数据库咨询定制服务媒体合作数据库咨询 | 琳琳 18983288589（微信同号）会议合作 | 赖老师 13550291524（微信同号）园区合作 | 周老师 18725665133（微信同号）定制服务 | 陈老师 18908392210（微信同号）媒体合作 | 小薇 18908208341（微信同号）咨询定制 | 张煜15320494102（微信同号）咨询合作 | 袁弋18983687563（微信同号）点击阅读原文，申请药融云企业版免费试用！

创新药小分子药物蛋白降解靶向嵌合体