更新于：2024-11-01

PRDX6

更新于：2024-11-01

基本信息

别名

1-Cys、1-Cys peroxiredoxin、1-Cys PRX

+ [21]

简介

Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (PubMed:9497358, PubMed:10893423). Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides (PubMed:10893423). Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (PubMed:10893423, PubMed:26830860). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (PubMed:10893423). Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (PubMed:10893423). Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:26830860). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (PubMed:26830860).

关联

项与 PRDX6 相关的药物

PIP-2

靶点

CYBB x PRDX6

作用机制

CYBB抑制剂 [+1]

在研机构

Peroxitech Therapeutics, Inc.

原研机构

University of Pennsylvania

在研适应症

急性肺损伤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PRDX6 相关的临床结果

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100 项与 PRDX6 相关的转化医学

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0 项与 PRDX6 相关的专利（医药）

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1,030

项与 PRDX6 相关的文献（医药）

2025-01-01·Meat Science

Spatial metabolomics, LC-MS and RNA-Seq reveal the effect of red and white muscle on rabbit meat flavor

Article

作者: Song, Bing ; Li, Zhen ; Zhu, Tongyan ; Solomon, Ahamba Ifeanyi ; Dong, Xianggui ; Song, Guohua ; Wang, Shuhui ; Ren, Zhanjun

Meat quality is a key factor influencing consumer purchasing decisions. Muscle composition consists of various types of myofibers (type I and type IIa, IIb, IIx myofibers), and the relative composition of fiber types has a significant impact on the overall biochemical properties and flavor of fresh meat. However, the relationship between biochemical changes in myofibers and their impact on meat quality remains underexplored. In this study, we compared the differences in meat quality by examining different muscles in rabbits, each containing different muscle fiber types. We focused on the adductor (ADD) and semitendinosus (ST) as our research subjects and investigated skeletal muscle metabolism at the individual myofibers level using Spatial metabolomics. Additionally, we utilized LC-MS and RNA-Seq to explore the molecular mechanisms underlying the metabolic differences between red and white muscle fibers. Our findings demonstrated that variations in myofiber composition significantly influenced meat color, pH, water content, and drip loss. Spatial metabolomics analysis identified 22 unique red and white muscle fingerprint metabolites, while LC-MS analysis revealed 123 differential metabolites, and these differential metabolites were mainly enriched in the pathways of ABC transporters, Biosynthesis of amino acids, glutathione metabolism, and arginine biosynthesis. To further elucidate the molecular mechanism of differential metabolism in ADD and ST, we identified 2248 differentially expressed genes (DEGs) by RNA-Seq and then combined DEGs with DMs for joint analysis. We found that red muscle exhibited higher levels of metabolites such as L-glutamic acid, glutathione, ascorbate, ornithine, oxidized glutathione, gamma-L-glutamyl-L-cysteine, cysteinylglycine, fumaric acid, gamma-aminobutyric acid. Additionally, related metabolic genes such as MGST1, ODC1, MGST3 and PRDX6 were highly expressed in ST muscle. These metabolites and genes were enriched in the glutathione and nicotinamide pathways, and had significant effects on meat color and drip loss. Moreover, red muscle contained more flavor compounds and nutrients, including adenosine monophosphate (AMP), ornithine, citrulline, taurine, acetyl phosphate, L-glutamic acid metabolites, as well as taurine and hypotaurine metabolites. Our results demonstrate that fresh meat with a higher proportion of red muscle fibers exhibited superior meat quality, enhanced flavor, and higher nutrient content. Furthermore, red muscle contains more antioxidant metabolites that can effectively prevent meat oxidation during the production process.

2024-12-01·Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

Peroxiredoxin 6 (Prx6) of Penaeus vannamei and effect of phenanthrene on Prx6 and glutathione peroxidase 4 expression, glutathione-dependent peroxidase activity and lipid peroxidation

Article

作者: Camacho-Jiménez, Laura ; Leyva-Carrillo, Lilia ; Peregrino-Uriarte, Alma B ; Gómez-Jiménez, Silvia ; Peregrino-Uriarte, Alma B. ; Yepiz-Plascencia, Gloria

Polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (PHE), are common pollutants found in coastal areas where shrimp farming is developed. Even though PAHs can have adverse effects on physiology, shrimp can detoxify and metabolize toxic compounds and neutralize the reactive oxygen species (ROS) produced during this process. This requires the activation of multiple antioxidant enzymes, including peroxiredoxin 6 (Prx6). Prx6 uses glutathione (GSH) to reduce phospholipid hydroperoxides, a function shared with GSH peroxidase 4 (GPx4). Prx6 has been scarcely studied in crustaceans exposed to pollutants. Herein, we report a novel Prx6 from the shrimp Penaeus vannamei that is abundantly expressed in gills and hepatopancreas. To elucidate the involvement of Prx6 in response to PAHs, we analyzed its expression in the hepatopancreas of shrimp sub-lethally exposed to PHE (3.3 μg/L) and acetone (control) for 24, 48, 72, and 96 h, along with GPx4 expression, GSH-dependent peroxidase activity, and lipid peroxidation (indicated by TBARS). We found that GPx4 expression is not affected by PHE, but Prx6 expression and peroxidase activity decreased during the trial. This might contribute to the rise of TBARS found at 48 h of exposure. However, maintaining GPx4 expression could aid to minimize lipid damage during longer periods of exposure to PHE.

2024-11-01·Free Radical Biology and Medicine

On the binding of auranofin to Prdx6 and its potential role in cancer cell sensitivity to treatment

Article

作者: Miyamoto, Sayuri ; Lima, Rodrigo S ; Inague, Alex ; Netto, Luís Eduardo S ; F. de Paiva, Raphael E. ; Lima, Rodrigo S. ; Viviani, Lucas G. ; Iijima, Thais S ; Angeli, José Pedro F ; Angeli, José Pedro F. ; Alegria, Thiago G P ; Netto, Luís Eduardo S. ; de Paiva, Raphael E F ; Nakahata, Douglas H ; Viviani, Lucas G ; Nakahata, Douglas H. ; Iijima, Thais S. ; Alegria, Thiago G.P.

In this study, we demonstrate that ferroptosis is a component of the cell death mechanism induced by auranofin in HT-1080 cells, in contrast to the gold(III) compounds [Au(phen)Cl₂]PF₆ and [Au(bnpy)Cl₂]. Additionally, we identify a potential role of Prdx6 in modulating the sensitivity of A-375 cells to auranofin treatment, whereas the gold(III) compounds evaluated here exhibit Prdx6-independent cytotoxicity. Finally, using mass spectrometry, we show that auranofin binds selectively to the catalytic Cys47 residue of Prdx6 in vitro under acidic conditions. No binding was observed with the C47S mutant or at neutral pH.

项与 PRDX6 相关的新闻（医药）

2024-08-09

·微信

免疫逃逸新机制！复旦大学发文：揭示肝癌治疗新靶点

【导读】肝细胞癌(HCC)是一种常见的恶性肿瘤，具有复杂的免疫逃逸机制，给治疗带来了挑战。S100A10基因在多种肿瘤中的作用已引起广泛关注。 8月8日，复旦大学研究团队在期刊《Cell Death&Disease》上发表了研究论文，题为“Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis”，本研究旨在阐明S100A10通过cPLA2和5-LOX轴对CD8+ T细胞耗竭的影响，从而阐明其在肝癌免疫逃逸中的作用。通过分析GEO和TCGA数据库中HCC相关数据，研究人员识别了与脂质代谢相关的差异表达基因，并建立了预后风险模型。随后，通过RNA-seq和PPI分析，研究人员确定了与CD8+ T细胞浸润显著相关的重要脂质代谢基因和下游因子S100A10, ACOT7和SMS。鉴于表达差异最显著，研究人员选择S100A10进行进一步研究。研究人员发现S100A10在肝癌组织中显著高表达，并可能通过cPLA2和5-LOX轴调节CD8+ T细胞耗竭和脂质代谢重编程。沉默S100A10可抑制CD8+ T细胞耗竭，进一步抑制肝癌的免疫逃逸。S100A10可能通过激活cPLA2和5-LOX轴，启动脂质代谢重编程，上调LTB4水平，从而促进肝癌组织中CD8+ T细胞耗竭，促进肝癌细胞的免疫逃逸，最终影响肝癌细胞的生长和迁移。本研究揭示了S100A10通过cPLA2和5-LOX轴在HCC免疫逃逸中的关键作用，为HCC的诊断和治疗提供了新的理论基础和潜在靶点。 https://www.nature.com/articles/s41419-024-06895-0#Sec34 背景知识 01 肝细胞癌(HCC)是世界范围内最常见的恶性肿瘤之一，是肝癌的主要形式。这类癌症主要与慢性乙型和丙型肝炎病毒感染、酒精性肝病和非酒精性脂肪性肝病有关。肝癌的诊断和治疗一直是医学界的难题。由于在最初阶段没有明确的症状，相当多的患者在诊断时已经进展到晚期，从而限制了替代治疗和预后。此外，HCC的变异性、肝脏解剖的复杂性和肿瘤的侵袭性进一步加剧了治疗的挑战。免疫逃逸在肝癌的发生发展中起着关键作用。肿瘤通过不同的机制抑制免疫系统的反应，例如，通过表达抑制T细胞活性的免疫抑制因子。然而，这一局限性不仅阻碍了传统免疫治疗的有效性，也为新型治疗方法的开发打开了大门，如特异性靶向PD-1/PD-L1通路的抑制剂。尽管在治疗和诊断方面存在挑战，但对潜在机制的全面理解，尤其是免疫逃逸，已经产生了新的治疗方法，并使人们乐观。生物信息学与RNA转录组测序(RNA-seq)的整合是生物医学研究的有力工具，能够全面识别基因表达模式，从而研究疾病机制和治疗靶点。在肝细胞癌(HCC)中，RNA-seq有效地识别了遗传异常和新的转录改变。这为深入了解HCC的发生、发展和转移提供了重要线索。通过生物信息学方法，本研究预测S100A10可能参与HCC。此外，该基因可能与肝癌的免疫逃逸有关，提示其参与抑制免疫反应和促进肿瘤生长。然而，S100A10在HCC免疫逃避中的作用尚不清楚。根据之前的文献，S100A10和cPLA2蛋白之间存在相互作用。cPLA2在细胞信号传递中起着至关重要的作用。如果激活不当，它会导致多种癌症的发生。因此，整合生物信息学和RNA-seq技术阐明了HCC的基本分子机制，并确定了S100A10作为一个有前景的治疗靶点。对S100A10和cPLA2相互作用的进一步研究将为HCC的治疗提供新的途径和方法。 S100A10可能与肝癌诱导的CD8+ T细胞耗竭有关 02 为了识别参与HCC中脂质代谢重编程的关键基因，研究人员从体外培养的MIHA肝细胞和MHCC97-L细胞中分别获取了3个正常样本和3个HCC样本，并进行了RNA-seq高通量测序和差异分析，共获得131个与脂代谢相关的差异表达基因。研究人员将RNA-seq得到的131个脂质代谢差异表达基因与用于构建Lasso模型的15个脂质代谢差异基因取交集，得到8个关键基因:S100A10、PRDX6、APEX1、SMS、ACSL3、ACOT7、PRKAA2和ME1。随后，研究人员进一步分析上述8个关键脂代谢基因与患者生存时间及CD8+ T细胞浸润的相关性。结果显示，这8个基因与患者的生存时间显著相关(均p < 0.01)，而仅S100A10、ACOT7和SMS与CD8+ T细胞浸润显著相关。研究人员进一步检测S100A10、ACOT7和SMS在两种正常肝细胞(MIHA、LX-2)和三种肝癌细胞(HCCLM3、Huh-7、MHCC97-L)中的mRNA和蛋白表达水平。结果显示，与正常肝细胞相比，肝癌细胞中S100A10、ACOT7和SMS的mRNA和蛋白表达均显著上调，其中S100A10的差异最为显著。据报道，S100A10在包括HCC在内的多种癌组织中高表达，并促进癌细胞的增殖和迁移。 S100A10与肝癌患者生存时间及CD8+ T细胞的相关性因此，研究人员认为S100A10可能是肝癌诱导CD8+ T细胞耗竭的关键因素。通过体内实验，研究人员发现沉默S100A10抑制了NOD-SCID小鼠肿瘤的生长和迁移，并恢复了肿瘤组织中CD8+ T细胞的功能，表明S100A10沉默有效抑制了肿瘤组织中CD8+ T细胞的耗竭，从而抑制了肝癌细胞的免疫逃逸。既往研究表明，T细胞耗竭在免疫功能紊乱和肿瘤免疫逃逸中发挥重要作用。在所有肿瘤浸润淋巴细胞中，CD8+ T细胞是通过执行T细胞受体介导的杀伤恶性细胞来进行抗肿瘤免疫的主要亚群。CD8+ T细胞浸润与肿瘤患者总生存率的提高之间的相关性已被充分证实。S100A10有望成为肝细胞癌新的治疗靶点。研究小结 03 综上，研究人员初步提出以下假设：S100A10可能激活cPLA2和5-LOX-LOX轴，其中信号激活导致脂质代谢重编程，上调LTB4水平，从而促进HCC组织中CD8+T细胞耗竭，导致HCC细胞免疫逃逸，最终影响HCC细胞的生长和迁移。本研究为治疗HCC提供了新的视角和一定理论依据。参考资料：https://www.nature.com/articles/s41419-024-06895-0#Sec34 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

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