更新于：2024-05-01

STEAP4

STEAP4 metalloreductase

更新于：2024-05-01

基本信息

别名

FLJ23153、Metalloreductase STEAP4、SchLAH

+ [8]

简介

Integral membrane protein that functions as NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane. Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (PubMed:30337524). Can also reduce Cu(2+) to Cu(1+) (By similarity). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (By similarity). Associated with obesity and insulin-resistance (PubMed:18430367, PubMed:18381574). Involved in inflammatory arthritis, through the regulation of inflammatory cytokines (PubMed:19660107). Inhibits anchorage-independent cell proliferation (PubMed:19787193).

关联

100 项与 STEAP4 相关的临床结果

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100 项与 STEAP4 相关的转化医学

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0 项与 STEAP4 相关的专利（医药）

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180

项与 STEAP4 相关的文献（医药）

2024-01-29·Biochemical and biophysical research communications

Ceftriaxone averts neuroinflammation and relieves depressive-like behaviors via GLT-1/TrkB signaling.

Article

作者: Ruyan Gao ; Tahir Ali ; Zizhen Liu ; Axiang Li ; Liangliang Hao ; Liufang He ; Xiaoming Yu ; Shupeng Li

The beneficial effect of a beta-lactam antibiotic, Ceftriaxone (CEF), to improve depressive-like symptoms has been documented previously, attributed to its modulation of glutamate neurotransmission. Here, we aimed to determine whether CEF could improve LPS-altered glutamatergic signaling associated with neuroinflammation-allied depression. To assess our goals, we established a neuroinflammation-allied depression mice model by injecting lipopolysaccharides (LPS), followed by behavioral and biochemical analysis. LPS-treated mice displayed depressive symptoms, neuroinflammation, dysregulated glutamate and its transporter (GLT-1) expression, altered expression of astrocyte reactive markers (GFAP, cxcl10, steap4, GBP2, and SRGN), and dysregulated BDNF/TrkB signaling. However, these changes were rescued by CEF treatment, as we found decreased neuroinflammation, relief of depression symptoms, and improved GLT-1 and BDNF/TrkB signaling upon CEF treatment. Moreover, GLT-1 and BDNF/TrkB regulation role of CEF was validated by K252a and DHK treatment. In summary, the anti-depressive effects of glutamate modulators, like CEF, are closely related to their anti-inflammatory role.

2024-01-08·BMC medical genomics

A novel prognostic signature and therapy guidance for hepatocellular carcinoma based on STEAP family.

Article

作者: Dongxue Fu ; Xian Zhang ; Yi Zhou ; Shanshan Hu

BACKGROUND:

The six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy.

METHODS:

Biological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R.

RESULTS:

We established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (- 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis.

CONCLUSIONS:

The novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification.

2024-01-01·International journal of biological sciences

Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia.

Article

作者: Renqian Feng ; Di Wang ; Tiantian Li ; Xulin Liu ; Tingwei Peng ; Mingchuan Liu ; Gaotong Ren ; Haowei Xu ; Haixia Luo ; Denghui Lu ; Bingchao Qi ; Mingming Zhang ; Yan Li

Iron homeostasis is crucial for optimal cardiac function. Iron deficiency and overload have been linked to the development of cardiomyopathy and heart failure (HF) via intricate mechanisms. Although the crucial role of SLC40A1 in iron metabolism by facilitating the efflux of cellular iron has been confirmed, its specific molecular functions in cardiovascular diseases remain poorly understood. In this study, we generated mice with inducible cardiomyocyte-specific overexpression of SLC40A1 for the first time. The overexpression of SLC40A1 in the cardiomyocytes of adult mice resulted in significant iron deficiency, leading to mitochondrial dysfunction, oxidative stress, and apoptosis, subsequently resulting in the development of fatal HF. Notably, SLC40A1 upregulation was observed in the ischemic region during the initial phase of myocardial infarction (MI), contributing to iron loss in the cardiomyocytes. Conversely, the cardiomyocyte-specific knockdown of SLC40A1 improved cardiac dysfunction after MI by enhancing mitochondrial function, suppressing oxidative stress, and reducing cardiomyocytes apoptosis. Mechanistically, Steap4 interacted with SLC40A1, facilitating SLC40A1-mediated iron efflux from cardiomyocytes. In short, our study presents evidence for the involvement of SLC40A1 in the regulation of myocardial iron levels and the therapeutic benefits of cardiomyocyte-specific knockdown of SLC40A1 in MI in mice.

项与 STEAP4 相关的新闻（医药）

2024-03-18

·生物谷

Int J Biol Sci：SLC40A1升高会损害心功能，加剧缺血心肌的线粒体功能障碍、氧化应激和细胞凋亡

这是第一个证明缺血心肌中SLC40A1上调引起的铁损失通过加剧线粒体功能障碍、氧化应激和细胞凋亡而加重心肌损伤的研究。心力衰竭(HF)是一个重要的全球公共卫生问题，由于其高患病率、死亡率和住院率，它深刻地影响着个人的福祉。铁在支持心肌细胞的高能需求中起着至关重要的作用，因为它能够有效地传递电子并促进各种重要的生化反应。值得注意的是，系统补铁在增加心肌铁含量方面的有效性是有限的。心肌铁含量升高经常发生在再灌注后，特别是当缺血再灌注(I/R)损伤导致微血管损伤时。然而，最近的一项研究表明，铁螯合剂的施用并不能减少I/R的梗死面积。然而，缺铁可加重I/R损伤。心肌缺血和I/R是不同的病理现象。然而，铁在缺血性心肌细胞中的作用尚不清楚。因此，心肌梗死后有效平衡心肌细胞铁水平的问题值得进一步研究和讨论。图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38169607/ 近日，来自空军医科大学的研究者们在Int J Biol Sci.杂志上发表了题为“Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia”的文章，该研究提供了SLC40A1参与心肌铁水平调节的证据，以及心肌细胞特异性敲低SLC40A1对小鼠心肌梗死的治疗益处。铁稳态对心脏功能的优化至关重要。铁缺乏和超载通过复杂的机制与心肌病和心力衰竭(HF)的发展有关。虽然SLC40A1通过促进细胞铁的外排在铁代谢中的关键作用已被证实，但其在心血管疾病中的具体分子功能仍知之甚少。在本研究中，研究者首次产生了诱导心肌细胞特异性过表达SLC40A1的小鼠。SLC40A1在成年小鼠心肌细胞中的过度表达导致明显的铁缺乏，导致线粒体功能障碍、氧化应激和细胞凋亡，进而导致致命性HF的发生。值得注意的是，在心肌梗死(MI)初始阶段，在缺血区域观察到SLC40A1上调，导致心肌细胞铁流失。相反，心肌细胞特异性敲低SLC40A1通过增强线粒体功能、抑制氧化应激和减少心肌细胞凋亡来改善心肌梗死后的心功能障碍。在机制上，Steap4与SLC40A1相互作用，促进SLC40A1介导的铁从心肌细胞外排。缺血诱导的SLC40A1和Steap4上调加剧线粒体功能障碍、氧化应激和细胞凋亡的途径，从而促进心力衰竭的进展的示意图图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38169607/ 综上所述，这是第一个证明缺血心肌中SLC40A1上调引起的铁损失通过加剧线粒体功能障碍、氧化应激和细胞凋亡而加重心肌损伤的研究。在机制上，Steap4与SLC40A1相互作用，促进铁的外排。此外，研究者发现心肌细胞特异性的SLC40A1过表达可导致小鼠致死性HF。因此，靶向SLC40A1可能为心肌梗死后HF提供新的治疗策略。(生物谷 Bioon.com）参考文献: Renqian Feng et al. Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia. Int J Biol Sci. 2024 Jan 1;20(2):414-432. doi: 10.7150/ijbs.89368.

2023-06-19

·药研网

前列腺癌新靶点：STEAP1

2020年全球癌症数据统计中，前列腺癌（PCa）的发病率占比第四，仅次于乳腺癌、肺癌和结直肠癌。根据去年国家癌症中心发布的中国和美国癌症统计数据，全人群男性前列腺癌的发病率在持续上升。2022中国前列腺癌发病人数约12.6万，死亡人数约5.6万；美国前列腺癌发病人数21.7万，死亡人数3.5万，以上均为男性。其中美国男性中最常见的就是前列腺癌。近年来，随着对细胞免疫治疗研究的不断深入，人们发现，前列腺癌中有多种相关抗原对前列腺癌的发生发展及预后产生影响，例如之前介绍过的前列腺特异性膜抗原（PSMA），以及今天要介绍的前列腺六跨膜上皮抗原1（STEAP1）。01STEAP1概述STEAP1属于前列腺六跨膜上皮抗原（STEAP）家族，该家族除STEAP1外，还有STEAP2、STEAP3、STEAP4，他们参与许多生物过程，包括细胞凋亡和增殖、氧化应激及胞内外分子运输。已有研究证明，STEAP1、STEAP2和STEAP4在PCa中过表达，而STEAP3在PCa中表达下降。STEAP1最早被发现，目前研究的最深入，其在许多组织中都有表达，但其在前列腺癌分泌性上皮细胞中的表达水平更高。STEAP1–4 在前列腺癌中的致癌作用（https://doi-org.libproxy1.nus.edu.sg/10.3390/cancers14164034）STEAP1由6个跨膜螺旋组成，包含339个氨基酸，具有胞内N端和C端结构域，由三个细胞外环和两个细胞内环连接。与其他的STEAP不同的是，STEAP1缺乏N末端NADPH-氧化还原酶（FNO）结构域，因此STEAP1不独立的表现出Fe3+或Cu2+还原酶活性，C端包含一个b型血红素辅助因子。 STEAP 基因组织、mRNA 转录本和蛋白质结构https://atlasgeneticsoncology.org/gene/44482/有数据显示，STEAP1在恶性前列腺组织中过表达，但在正常的前列腺组织中表达较低，因此STEAP1是一个理想的治疗靶点。此外，STEAP1可作为诊断和预后生物标志物。有研究发现，与健康男性相比，PCa患者的STEAP1阳性细胞外囊泡水平显著升高且STEAP1过表达与生化复发之间有显著关联。STEAP1在肿瘤和正常组织中的表达情况（http://gepia.cancer-pku.cn/detail.php?gene=STEAP1）吉满生物推出构建STEAP1过表达稳定细胞系/抗体的服务（详细数据见文末），充分满足药物研发需求，助力药物临床申报。02在研进展目前STEAP1药物还处于临床开发阶段，其中89Zr-DFO-MSTP2109A和AMG 509已经进入临床。89Zr-DFO-MSTP2109A89Zr-DFO-MSTP2109A是由Genentech, Inc.和Memorial Sloan Kettering Cancer Center联合研制的靶向 STEAP1的放射性标记抗体。目前89Zr-DFO-MSTP2109A已完成临床1/2期试验，具有良好的耐受性，并在转移性去势抵抗性前列腺癌（mCRPC）患者骨骼和软组织中显示出出色的可视化效果，因此可作为STEAP-1 定向治疗的潜在预测生物标志物。AMG 509AMG509由Amgen通过Xencor的Xmab 2+1非对称技术开发而成。AMG509包括两个相同的人源化抗STEAP1 Fab结构域和一个抗CD3 scFv结构域，其中抗CD3 scFv结构域与一端的STEAP1 Fab结构域偶联。Fc结缺乏Fc效应功能以提高安全性，另一方面则提高与FcRn的结合并延长血清半衰期。在体内模型中，AMG 509在前列腺癌和尤文肉瘤异种移植模型中具有较强的抗肿瘤活性，并伴随肿瘤中CD8+T细胞的活化和扩增。0.01mg/kg AMG 509治疗可抑制80%及以上的肿瘤生长。AMG 509目前处于临床I期，同时今年3月份，安进和百济神州共同提交的国内临床申请也获CDE受理，是国内首款申报临床的CD3/STEAP1双抗。用心做好细胞，为更好的靶向药吉满生物科技（上海）有限公司，是位于上海浦东的一家以创新为驱动的工程化细胞系研发公司，基于自有的国内最大报告基因平台、慢病毒平台以及最迅速的药研网资讯平台，目前已构建出500余株现货单克隆细胞系产品，覆盖ROR1/DLL3/SLC39A6/TROP2/BCMA/BDCA/TREM2……200余新药热门靶点，其中有90余靶点开发有对应luciferase reporter方法，更有国内独家/首家CCR8, BDCA, TREM2和GAPR等luciferase的assay平台。STEAP1细胞系/抗体产品列表部分结果：GM-C21519：H_STEAP1 CHO-K1 Cell Line使用Anti-H_STEAP1 hIgG1 Antibody(Vandortuzumab)（Genomeditech/GM-33026AB）流式验证结果GM-C21520：H_STEAP1 HEK-293 Cell Line使用Anti-H_STEAP1 hIgG1 Antibody(Vandortuzumab)（Genomeditech/GM-33026AB）流式验证结果GM-C21521 ：Cynomolgus_STEAP1 CHO-K1 Cell Line使用Anti-H_STEAP1 hIgG1 Antibody(Vandortuzumab)（Genomeditech/GM-33026AB）流式验证结果吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域近200余个靶点。2020年底成立专业细胞系子品牌DDXCELL，同时已建立了DDXCELL现货查询小程序。截止当前已布局近200个热门靶向药靶点500余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。细胞系现货查询请扫码👇

信使RNA临床研究临床结果