The Biology of Peroxiredoxin 6

过氧化还原蛋白 6 的生物学

基本信息

项目摘要

Project Summary/Abstract Peroxiredoxin 6 (Prdx6) is a multi-functional enzyme that expresses glutathione peroxidase, phospholipase A2 (PLA2), and lysophosphatidylcholine acyltransferase (LPCAT) activities in separate catalytic sites. Prdx6 can reduce phospholipid hydroperoxides and hydrolyze and re-acylate phospholipid fatty acyl bonds. Prdx6 is, therefore, a complete enzyme for the repair of peroxidized cell membranes. Prdx6 has been implicated in several pathophysiological conditions, including acute lung injury, inflammation, carcinogenesis, various chronic central nervous system diseases, retinal disease, type 2 diabetes, muscle atrophy, and male infertility, but basic questions about the biology of this unique enzyme remain unanswered. Our preliminary data strongly suggest that Prdx6 suppresses ferroptosis, an iron-dependent form of regulated cell death driven by the accumulation of phospholipid hydroperoxides. Emerging evidence implicates ferroptosis in several degenerative diseases, carcinogenesis, stroke, traumatic brain injury, and ischemia/reperfusion injury, among others. Hence, establishing the mechanisms and physiological relevance of ferroptosis regulation by Prdx6 is crucial. My lab is interested in studying the role of the glutathione peroxidase, PLA2, and LPCAT activities of Prdx6 on the regulation of ferroptosis induced by inhibition of cystine uptake, hypoxia/reoxygenation, and oxygen toxicity. We will use mice and cells with single point mutations that inactivate each of the activities of Prdx6 without affecting the others, along with state-of-the-art analytical tools to dissect the role of this enzyme on the regulation of ferroptosis. In a second project, I propose to study the role of Prdx6 in the maintenance of mitochondrial function. Our preliminary data show that Prdx6 deficiency alters transcriptional signatures of mitochondrial metabolism and reduces mitochondrial respiration. We will study the effects of the catalytic activities of Prdx6 on mitochondrial morphology, dynamics, and function using extracellular flux assays and three-dimensional imaging techniques. The results of this proposal will contribute to our understanding of one of the critical mediators of cellular redox balance. These results will also provide essential information for future translational strategies for the prevention and treatment of diseases associated with dysregulated redox homeostasis.
项目总结/摘要 Peroxiredoxin 6(Prdx6)是一种多功能酶,表达谷胱甘肽过氧化物酶、磷脂酶A2 (PLA2)和溶血磷脂酰胆碱酰基转移酶(LPCAT)活性。Prdx6可以 减少磷脂过氧化氢并水解和再酰化磷脂脂肪酰基键。Prdx6是, 因此,一种完整的酶用于修复过氧化的细胞膜。Prdx6被卷入了 几种病理生理状况,包括急性肺损伤、炎症、癌变、各种 慢性中枢神经系统疾病、视网膜疾病、2型糖尿病、肌肉萎缩和男性不育, 但关于这种独特酶的生物学基本问题仍然没有答案。我们的初步数据显示 这表明Prdx6抑制铁凋亡,这是一种铁依赖性形式的受调节的细胞死亡, 磷脂过氧化氢的积累。新出现的证据表明, 退行性疾病、致癌作用、中风、创伤性脑损伤和缺血/再灌注损伤, 他人因此,建立Prdx6调节铁凋亡的机制和生理相关性, 至关重要的.我的实验室有兴趣研究谷胱甘肽过氧化物酶,PLA2和LPCAT活性的作用, Prdx6对胱氨酸摄取抑制、缺氧/复氧和缺氧/复氧诱导的铁凋亡的调节作用 氧中毒我们将使用具有单点突变的小鼠和细胞,这些单点突变会抑制 Prdx 6而不影响其他酶,沿着最先进的分析工具来剖析这种酶的作用 对铁下垂的调节作用。在第二个项目中,我建议研究Prdx6在维护 线粒体功能我们的初步数据表明,Prdx6缺陷改变了 线粒体代谢和减少线粒体呼吸。我们将研究催化剂的作用 Prdx6对线粒体形态、动力学和功能的活性,使用细胞外通量测定, 三维成像技术。这项建议的结果将有助于我们了解一个 细胞氧化还原平衡的关键介质。这些结果也将为未来的研究提供必要的信息。 用于预防和治疗与氧化还原失调相关的疾病的转化策略 体内平衡

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Jose P Vazquez Medina其他文献

Jose P Vazquez Medina的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Jose P Vazquez Medina', 18)}}的其他基金

The role of lysophosphatidic acid signaling in lung ischemia/reperfusion injury
溶血磷脂酸信号在肺缺血/再灌注损伤中的作用
  • 批准号:
    9070355
  • 财政年份:
    2015
  • 资助金额:
    $ 37.68万
  • 项目类别:

相似海外基金

Greasing endocytosis in plants - understanding the role of S-acylation in receptor kinase function and internalisation
植物中的润滑内吞作用 - 了解 S-酰化在受体激酶功能和内化中的作用
  • 批准号:
    BB/Y003756/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Research Grant
Ghrelin de-acylation inhibitors as novel compounds for Parkinson's dementia
生长素释放肽去酰化抑制剂作为治疗帕金森痴呆症的新型化合物
  • 批准号:
    MR/Y503435/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Research Grant
S-acylation-dependent regulation of cytokine receptor signaling and cardiac maladaptation
细胞因子受体信号传导和心脏适应不良的 S-酰化依赖性调节
  • 批准号:
    10561406
  • 财政年份:
    2023
  • 资助金额:
    $ 37.68万
  • 项目类别:
Comprehensive analysis of acidic patch binder using histone acylation catalysts
使用组蛋白酰化催化剂综合分析酸性贴片粘合剂
  • 批准号:
    22KJ1113
  • 财政年份:
    2023
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
S-Acylation of transmembrane proteins in the early secretory pathway
早期分泌途径中跨膜蛋白的 S-酰化
  • 批准号:
    BB/X001504/1
  • 财政年份:
    2023
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Research Grant
N-terminal acylation and sorting of Helicobacter pylori lipoproteins and their role in host response to infection
幽门螺杆菌脂蛋白的 N 末端酰化和分选及其在宿主感染反应中的作用
  • 批准号:
    10584620
  • 财政年份:
    2022
  • 资助金额:
    $ 37.68万
  • 项目类别:
The Molecular Mechanisms of Glycolytic Enzyme S-acylation in Neurons
神经元糖酵解酶S-酰化的分子机制
  • 批准号:
    576016-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Anti-CRISPR-mediated Acylation and Bioreversible Esterification for Precision Genome Editing
用于精准基因组编辑的抗 CRISPR 介导的酰化和生物可逆酯化
  • 批准号:
    10657417
  • 财政年份:
    2022
  • 资助金额:
    $ 37.68万
  • 项目类别:
High Throughput Screen for Inhibitors of the YEATS2 Histone Acylation Reader
YEATS2 组蛋白酰化酶抑制剂的高通量筛选
  • 批准号:
    10389517
  • 财政年份:
    2022
  • 资助金额:
    $ 37.68万
  • 项目类别:
Roles of KAT8 complexes in governing histone acylation and mouse cerebral development
KAT8复合物在控制组蛋白酰化和小鼠大脑发育中的作用
  • 批准号:
    RGPIN-2019-07122
  • 财政年份:
    2022
  • 资助金额:
    $ 37.68万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了