Redox Biochemistry and Chemistry最新文献

Uratylated albumin activates endothelial cells to induce monocyte adhesion and the release of pro-inflammatory cytokines 尿酰化白蛋白激活内皮细胞，诱导单核细胞粘附和促炎细胞因子的释放

Redox Biochemistry and Chemistry

Pub Date : 2026-01-19 DOI: 10.1016/j.rbc.2026.100071

Railmara Pereira da Silva , Beatriz Pereira da Silva , Antônio Paulo Siqueira Pratti , Bianca Dempsey , Caroline Dutra Lacerda , Gustavo Penteado Battesini Carretero , Álbert Souza Peixoto , Litiele Cezar Cruz , Camilla Adan , Iolanda Midea Cuccovia , Flavia Carla Meotti

Albumin, the most abundant serum protein in mammals, is critical for transporting low-water-soluble metabolites, ions, and xenobiotics, as well as maintaining osmotic balance. This protein is highly susceptible to post-translational modifications, which can alter its structure and function. Reactive oxygen species (ROS) play a significant role in inducing such modifications, leading to protein dysfunction and contributing to inflammatory and cardiovascular pathologies. Previous studies have demonstrated a link between uric acid (UA) oxidation products, particularly urate hydroperoxide (HOOU), and albumin modifications through a process termed uratylation. These albumin adducts result from the addition of a 140 Da product mass predominantly on lysine and amine from N-terminal residues. Therefore, the aim of this study was to investigate the structural and functional consequences of uratylation on albumin and its effects on endothelial cells. Uratylation promotes a decrease in enthalpy change of denaturation of albumin and binding of Anilino-Naphthalene-Sulfonic acid (ANS), suggesting slight changes in protein structure. Uratylated albumin reduced human umbilical vein endothelial cell (HUVEC) migration, increased intercellular adhesion molecule-1 (ICAM-1) expression and, consequently, monocyte adhesion (THP-1), indicating endothelial activation. Furthermore, the presence of uratylated albumin stimulated the release of tumor necrosis factor-α (TNF-α). These findings provide novel insights into the mechanistic pathways connecting uric acid oxidation, post-translational modification on albumin and inflammation, highlighting the potential role of uratylated albumin in endothelial dysfunction and atherogenesis.

白蛋白是哺乳动物中最丰富的血清蛋白，对于运输低水溶性代谢物、离子和异种生物以及维持渗透平衡至关重要。这种蛋白质对翻译后修饰非常敏感，这可以改变其结构和功能。活性氧（ROS）在诱导这种修饰，导致蛋白质功能障碍和促进炎症和心血管疾病中发挥重要作用。以前的研究已经证明了尿酸（UA）氧化产物，特别是尿酸氢过氧化物（HOOU）和白蛋白修饰之间的联系，这一过程被称为尿酸基化。这些白蛋白加合物是在n端残基的赖氨酸和胺的基础上添加140 Da的产物。因此，本研究的目的是研究尿酰化对白蛋白的结构和功能影响及其对内皮细胞的影响。Uratylation促进了白蛋白变性焓变的降低和苯胺-萘磺酸（anilino - naphthale -磺酸，ANS）的结合，表明蛋白质结构发生了轻微的变化。尿毒化白蛋白减少人脐静脉内皮细胞（HUVEC）迁移，增加细胞间粘附分子-1 （ICAM-1）表达，从而增加单核细胞粘附（THP-1），表明内皮细胞活化。此外，尿酰化白蛋白的存在刺激了肿瘤坏死因子-α (TNF-α)的释放。这些发现为尿酸氧化、白蛋白翻译后修饰和炎症之间的机制通路提供了新的见解，强调了尿酰化白蛋白在内皮功能障碍和动脉粥样硬化中的潜在作用。

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引用次数: 0

Evaluating real time intracellular redox toxicology using live-cell imaging approaches 利用活细胞成像方法评估实时细胞内氧化还原毒理学

Redox Biochemistry and Chemistry

Pub Date : 2026-01-07 DOI: 10.1016/j.rbc.2026.100070

Edward R. Pennington , Emma Kinerson , Syed Masood , Elizabeth M. Corteselli , James M. Samet

Intracellular oxidative stress is a common mechanism of cellular dysregulation as a result of supraphysiological levels of reactive oxygen species (ROS). Imbalances in redox homeostasis underly adverse responses arising from exposure to a wide variety of xenobiotics and environmental exposures. Observing oxidative cellular events in real time poses multiple analytical challenges, requiring sensitive and specific methodologies that are capable of detecting transient events with high spatiotemporal resolution. We review here the advantages that live-cell imaging offers as a non-destructive approach that is well suited for redox toxicology studies. The effectiveness of this approach is heavily reliant on the use of fluorescent redox sensitive probes, such as small molecule and genetically encoded sensors that report on specific ROS and redox couples. We discuss a variety of small molecule and genetically encoded sensors that are used in redox toxicology, as well as the caveats and limitations posed by their use.

细胞内氧化应激是活性氧（ROS）超生理水平导致细胞失调的常见机制。氧化还原内平衡的不平衡是暴露于各种各样的外源性药物和环境暴露所引起的不良反应的基础。实时观察氧化细胞事件带来了多重分析挑战，需要能够以高时空分辨率检测瞬态事件的敏感和特定方法。我们在这里回顾了活细胞成像作为一种非破坏性方法的优势，它非常适合于氧化还原毒理学研究。这种方法的有效性在很大程度上依赖于荧光氧化还原敏感探针的使用，如小分子和基因编码传感器，报告特定的ROS和氧化还原偶对。我们讨论了各种用于氧化还原毒理学的小分子和遗传编码传感器，以及它们的使用所带来的警告和限制。

引用次数: 0

Dietary phenolic compounds as modulators of AGEs-induced photo-oxidation: A focus on the skin and eye lens 膳食酚类化合物作为ages诱导的光氧化的调节剂：对皮肤和眼睛晶状体的关注

Redox Biochemistry and Chemistry

Pub Date : 2025-12-24 DOI: 10.1016/j.rbc.2025.100068

Felipe Ávila , Denis Fuentealba , Francisca Muñoz , Alejandra San Martin , Bertrand Friguet

Advanced glycation end products (AGEs) are irreversible products formed when long-lived proteins undergo non-enzymatic reactions with reducing sugars or reactive metabolites. These products resist proteolytic degradation and therefore accumulate with age. Some AGEs act as chromophores, absorbing UVA-visible light and initiating photosensitized oxidation, a process implicated in photoaging of tissues such as the eye lens and skin. Dietary polyphenols, known for their antioxidant and antiglycation effects, may also modulate AGE-mediated photosensitized reactions, although this remains poorly understood. This article discusses the mechanisms through which AGEs contribute to photo-oxidative damage in light-exposed tissues and discusses the potential of dietary polyphenols to modulate these photo-induced processes.

晚期糖基化终产物（AGEs）是长寿命蛋白质与还原糖或活性代谢物发生非酶反应时形成的不可逆产物。这些产物抵抗蛋白水解降解，因此随着年龄的增长而积累。一些AGEs充当发色团，吸收uva -可见光并引发光敏氧化，这一过程与眼晶状体和皮肤等组织的光老化有关。饮食中的多酚，以其抗氧化和抗糖化作用而闻名，也可能调节age介导的光敏反应，尽管这一点尚不清楚。本文讨论了AGEs在光暴露组织中促进光氧化损伤的机制，并讨论了膳食多酚调节这些光诱导过程的潜力。

引用次数: 0

In vivo studies of redox biochemistry in vertebrate tissues - present successes and future horizons 脊椎动物组织中氧化还原生物化学的体内研究-目前的成功和未来的前景

Redox Biochemistry and Chemistry

Pub Date : 2025-12-23 DOI: 10.1016/j.rbc.2025.100069

Lev L. Naumov , Anastasia D. Sergeeva , Veronika A. Katrukha , Alexander I. Kostyuk , Nadezda A. Brazhe , Dmitry S. Bilan , Yulia V. Khramova

Over the past decades, the field of redox biology has witnessed a profound expansion in the catalog of known redox-active compounds, revealing their critical roles in cellular signaling and homeostasis. Paralleling this discovery, the toolbox of genetically encoded fluorescent indicators (GEFIs) has evolved to enable real-time, specific monitoring of these molecules within living cells. This review synthesizes key studies employing GEFIs to investigate redox dynamics in vertebrate models, covering a spectrum of physiological and pathophysiological contexts. A critical analysis of the architectural designs, operational mechanisms, and performance parameters—including advantages and inherent limitations—of prominent GEFIs is provided. Finally, we explore the constraints of traditional fluorescence imaging methodologies in complex in vivo settings and consider label-free methods for detecting redox events using Raman spectroscopy, FLIM.

在过去的几十年里，氧化还原生物学领域见证了已知氧化还原活性化合物目录的深刻扩展，揭示了它们在细胞信号传导和体内平衡中的关键作用。与此同时，基因编码荧光指示器（gefi）的工具箱已经发展到能够实时、特定地监测活细胞内的这些分子。本文综述了利用gefi研究脊椎动物模型中氧化还原动力学的关键研究，涵盖了生理和病理生理背景。本文对主要gefi的架构设计、操作机制和性能参数（包括优势和固有局限性）进行了批判性分析。最后，我们探讨了传统荧光成像方法在复杂体内环境中的局限性，并考虑使用拉曼光谱（FLIM）检测氧化还原事件的无标记方法。

引用次数: 0

Influence of the peptide bond and the presence of tryptophan on the photogeneration and photochemical properties of dityrosine 肽键和色氨酸的存在对二酪氨酸的光生成和光化学性质的影响

Redox Biochemistry and Chemistry

Pub Date : 2025-12-22 DOI: 10.1016/j.rbc.2025.100067

Karla P. García Beltrán , Gemma M. Rodríguez-Muñiz , Virginie Lhiaubet-Vallet , Andrés H. Thomas , M. Laura Dántola

3,3′-Dityrosine, resulting from the formation of a carbon-carbon bond between two tyrosines (Tyr), is one of the most important modifications of the oxidatively generated damage to proteins. Its formation can induce structural changes in proteins, leading to the loss of their biological function. Interestingly, under UVA radiation, dityrosine can also act as an intrinsic photosensitizer that generates reactive oxygen species and induces chemical modifications in amino acids. Despite the biomedical importance of dityrosine, the information regarding its photosensitized generation and photochemical properties is limited due to the drawbacks inherent to its synthesis. In this work we studied the photosensitized formation of dityrosine, in the absence and presence of tryptophan (Trp), using pterin (Ptr) as endogenous type I sensitizer. Free Tyr and Tyr incorporated into specially designed peptides were used as target molecules. Our results indicate that the efficiency of dimerization is not affected by the presence of the peptide bond. Nonetheless, incorporation of dityrosine into a peptide chain appears to confer a certain degree of protection, making it more resistant to photosensitized degradation. Moreover, we demonstrated that, within a peptide chain, an adjacent Trp residue promotes the photoinduced dimerization of Tyr, likely due to electron transfer from the Tyr residue to the oxidized Trp. This effect is not observed when the two residues are more distant. Additionally, the presence of free Trp or Trp within the same peptide chain enhances the efficiency of the photosensitized degradation of the free and peptide dityrosine, respectively.

3,3 ' -二酪氨酸是由两个酪氨酸（Tyr）之间的碳-碳键形成的，是氧化产生的蛋白质损伤中最重要的修饰之一。它的形成可以诱导蛋白质的结构变化，导致其生物功能的丧失。有趣的是，在UVA辐射下，二酪氨酸还可以作为一种内在光敏剂，产生活性氧并诱导氨基酸的化学修饰。尽管二酪氨酸具有重要的生物医学意义，但由于其合成固有的缺陷，有关其光敏生成和光化学性质的信息有限。在这项工作中，我们研究了在色氨酸（Trp）缺失和存在的情况下，以蝶呤（Ptr）作为内源性I型增敏剂，二酪氨酸的光敏化形成。游离酪氨酸和结合在特殊设计的肽中的酪氨酸作为靶分子。我们的结果表明，二聚化的效率不受肽键存在的影响。尽管如此，二酪氨酸结合到肽链中似乎具有一定程度的保护作用，使其更能抵抗光敏降解。此外，我们证明，在肽链中，相邻的Trp残基促进了Tyr的光诱导二聚化，可能是由于电子从Tyr残基转移到氧化的Trp。当两个残基距离较远时，则没有观察到这种效应。此外，自由色氨酸或同一肽链内色氨酸的存在分别提高了光敏降解自由和肽二酪氨酸的效率。

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引用次数: 0

Proteomic identification of protein radicals from myeloperoxidase-mediated mefenamic acid oxidation reveals a mechanism of NSAID-induced oxidative injury 髓过氧化物酶介导的甲胺酸氧化过程中蛋白质自由基的蛋白质组学鉴定揭示了非甾体抗炎药诱导氧化损伤的机制

Redox Biochemistry and Chemistry

Pub Date : 2025-11-14 DOI: 10.1016/j.rbc.2025.100066

Newton H. Tran , Steven Lockhart , Othman Eldalal , Phuong G. Tran , John-Paul R. Cooper , Lusine Tonoyan , Richard P. Fahlman , Arno G. Siraki

Mefenamic acid (MFA; Ponstel®, USA) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat inflammatory pain. Despite its effectiveness, it carries an FDA black box warning for serious adverse effects, including hepatotoxicity, agranulocytosis, and gastrointestinal injury. While these toxicities are often linked to oxidative distress, the molecular mechanisms remain poorly understood. A key interaction occurs between MFA and myeloperoxidase (MPO), a heme enzyme released from activated neutrophils during inflammation. MPO catalyzes MFA's one-electron oxidation, forming reactive metabolites that modify cellular macromolecules and potentially induce oxidative stress and immune-mediated cytotoxicity. This study examined whether MPO-mediated metabolism of MFA contributes to oxidative damage and cell death in HL-60 promyelocytic leukemia cells. Using compartment-specific spin probes and EPR spectroscopy, MFA was found to increase oxidant production in both cytosolic and mitochondrial compartments. MFA also caused an 80 % loss of mitochondrial membrane potential, activated the Nrf2 antioxidant response, and suppressed phospho-ERK1/2 signaling—changes significantly reversed by PF-1355, a selective MPO inhibitor. Immuno-spin trapping revealed a 133-fold increase in protein-centered radicals following MFA exposure, which was reduced by 97 % with MPO inhibition. Proteomic analysis identified MPO and HSPD1 among the most significantly modified proteins. These findings provide mechanistic insight that MPO-mediated oxidation of MFA generates reactive protein-free radicals, which disrupt redox signaling and protein integrity—ultimately contributing to mitochondrial dysfunction, oxidative stress, and cytotoxicity under inflammatory conditions. This mechanism provides insight into NSAID-induced oxidative injury and supports targeting MPO to improve drug safety under inflammatory conditions.

甲氧胺酸（MFA, Ponstel®，USA）是一种用于治疗炎症性疼痛的非甾体抗炎药（NSAID）。尽管它有效，但FDA对其严重的副作用（包括肝毒性、粒细胞缺乏症和胃肠道损伤）发出了黑盒警告。虽然这些毒性通常与氧化应激有关，但分子机制仍然知之甚少。一个关键的相互作用发生在MFA和髓过氧化物酶（MPO）之间，MPO是炎症期间由活化的中性粒细胞释放的血红素酶。MPO催化MFA的单电子氧化，形成修饰细胞大分子的活性代谢物，并可能诱导氧化应激和免疫介导的细胞毒性。本研究探讨了mpo介导的MFA代谢是否有助于HL-60早幼粒细胞白血病细胞的氧化损伤和细胞死亡。使用室特异性自旋探针和EPR光谱，发现MFA增加细胞质和线粒体室中氧化剂的产生。MFA还导致线粒体膜电位损失80%，激活Nrf2抗氧化反应，并抑制磷酸化- erk1 /2信号通路，这些变化被选择性MPO抑制剂PF-1355显著逆转。免疫自旋捕获显示，暴露于MFA后，蛋白中心自由基增加了133倍，而MPO抑制则减少了97%。蛋白质组学分析发现MPO和HSPD1是最显著的修饰蛋白。这些发现提供了mpo介导的MFA氧化产生反应性蛋白自由基的机制，这些自由基会破坏氧化还原信号和蛋白质完整性，最终导致炎症条件下的线粒体功能障碍、氧化应激和细胞毒性。这一机制为探究非甾体抗炎药诱导的氧化损伤提供了线索，并为靶向MPO提高炎症条件下的药物安全性提供了支持。

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引用次数: 0

Near UV and visible light photo-degradation of therapeutic proteins: reaction mechanisms and significance for the development of pharmaceutical formulations 近紫外和可见光下治疗性蛋白质的降解：反应机制及其对药物配方开发的意义

Redox Biochemistry and Chemistry

Pub Date : 2025-10-31 DOI: 10.1016/j.rbc.2025.100065

Christian Schöneich

In the biotechnology industry, scientists are becoming increasingly aware that therapeutic protein formulations are susceptible to photo-degradation by near UV and/or visible light. Especially the reaction mechanisms leading to photo-degradation by visible light exposure are frequently unclear; however, progress in the characterization of a few of these processes has been made and this review summarizes reaction mechanisms which can rationalize some of the visible light-dependent photo-degradation in pharmaceutical formulations of therapeutic proteins. It will become clear that the mechanisms of photo-degradation do not necessarily depend only on the nature of the protein but also on the nature of excipients and common impurities.

在生物技术行业，科学家们越来越意识到治疗性蛋白质配方容易受到近紫外线和/或可见光的光降解。特别是在可见光照射下导致光降解的反应机制往往不清楚；然而，在这些过程的表征方面已经取得了一些进展，本文综述了反应机制，可以使一些治疗性蛋白质药物配方中依赖可见光的光降解合理化。很明显，光降解的机制不仅取决于蛋白质的性质，还取决于赋形剂和常见杂质的性质。

引用次数: 0

Mapping oxylipin signatures in human diseases using LC-MS/MS 用LC-MS/MS绘制人类疾病中的氧脂质特征

Redox Biochemistry and Chemistry

Pub Date : 2025-10-17 DOI: 10.1016/j.rbc.2025.100063

Larissa R. Diniz , Rosangela S. Santos , Hector Oreliana , Ana Clara A. Zucão, Megumi N. Yukuyama, Guilherme R.S. Resende, Thais Satie Iijima, Lucas G. Viviani, Sayuri Miyamoto

Oxylipins, a diverse family of oxidized lipids derived from mono- and polyunsaturated fatty acids, are increasingly recognized as key mediators in redox biology and inflammation. They are produced through enzymatic pathways involving cyclooxygenases (COX), lipoxygenases (LOX), cytochrome P450s (CYP), and soluble epoxide hydrolase (sEH), as well as through non-enzymatic mechanisms including singlet oxygen and free radical-mediated lipid peroxidation. Advances in mass spectrometry, particularly targeted LC-MS/MS approaches, have enabled sensitive and selective quantification of oxylipins in complex biological matrices. This article provides a focused overview of oxylipin alterations in neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis), obesity, infectious diseases, chronic pain conditions, and inflammatory skin disorders.

氧脂素是一种由单不饱和脂肪酸和多不饱和脂肪酸衍生而来的氧化脂类，越来越被认为是氧化还原生物学和炎症的关键介质。它们通过环氧化酶（COX）、脂氧化酶（LOX）、细胞色素p450 （CYP）和可溶性环氧化物水解酶（sEH）等酶促途径产生，也通过单线态氧和自由基介导的脂质过氧化等非酶促机制产生。质谱技术的进步，特别是靶向LC-MS/MS方法，使复杂生物基质中氧化脂质的敏感和选择性定量成为可能。这篇文章重点概述了在神经退行性疾病（阿尔茨海默病、帕金森氏病、肌萎缩侧索硬化症和多发性硬化症）、肥胖、传染病、慢性疼痛状况和炎症性皮肤疾病中氧脂蛋白的改变。

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Deacetylation of SOD3 by sirtuins restores furin cleavage sirtuins使SOD3去乙酰化，恢复了furin的裂解

Redox Biochemistry and Chemistry

Pub Date : 2025-10-14 DOI: 10.1016/j.rbc.2025.100062

Emily C. Mitchem , Peter S. Harris , Cole R. Michel , Courtney D. McGinnis , Shashikant Ray , Krishna M.G. Mallela , James R. Roede , Steen V. Petersen , Eva S. Nozik , Kristofer S. Fritz

Accumulation of superoxide radicals leads to disrupted redox signaling and oxidative damage. The primary extracellular scavenger of superoxide is extracellular superoxide dismutase (SOD3), a crucial enzyme in maintaining antioxidant status and proper immune function. SOD3 distribution to the extracellular matrix is determined by the presence of a C-terminal heparin-binding domain (HBD). This region can be removed through intracellular proteolytic processing by furin. Cleavage of the HBD has been shown to be modulated by post-translational cysteine redox status, regulating the secretion of SOD3. Interestingly, other members of the SOD family, SOD1 and SOD2, are known to be inhibited by lysine acetylation, a metabolically linked post-translational modification (PTM) that can alter protein structure, function, and localization. Yet, no reports describe the effect of acetylation on SOD3. Here, immunoblotting and mass spectrometry (MS) were used to quantify the global and site-specific acetylation of recombinant human SOD3. Interestingly, a predicted and targeted parallel reaction monitoring (PRM) MS-based approach was necessary to identify lysine acetylation within the C-terminal HBD of SOD3. Acetylation was found to prevent furin cleavage with no impact on SOD3 activity. Our results also reveal that SOD3 is robustly deacetylated by NAD⁺-dependent sirtuins (SIRT1 and SIRT3), with moderate activity against K220 and high activity against K211 and K212 in the HBD furin cleavage region. These sites of acetylation have not been previously reported, likely due to the peptide's unique hydrophilic nature. Overall, our findings reveal that sirtuin-directed deacetylation of SOD3 restored furin cleavage, defining an important link between redox homeostasis and acetylation-directed metabolic regulation of extracellular oxidative stress.

超氧自由基的积累导致氧化还原信号中断和氧化损伤。细胞外超氧化物的主要清除者是细胞外超氧化物歧化酶（SOD3），这是维持抗氧化状态和适当免疫功能的关键酶。SOD3分布到细胞外基质是由c端肝素结合域（HBD）的存在决定的。这个区域可以通过胞内蛋白水解作用去除。研究表明，HBD的切割受翻译后半胱氨酸氧化还原状态的调节，从而调节SOD3的分泌。有趣的是，SOD家族的其他成员SOD1和SOD2被赖氨酸乙酰化所抑制，赖氨酸乙酰化是一种代谢相关的翻译后修饰（PTM），可以改变蛋白质的结构、功能和定位。然而，没有报道描述乙酰化对SOD3的影响。本研究采用免疫印迹法和质谱法（MS）来定量重组人SOD3的全局乙酰化和位点特异性乙酰化。有趣的是，需要一种基于预测和靶向的平行反应监测（PRM） ms的方法来鉴定SOD3 c端HBD内的赖氨酸乙酰化。发现乙酰化可以防止furin裂解，但对SOD3活性没有影响。我们的研究结果还表明，SOD3被NAD+依赖性sirtuins （SIRT1和SIRT3）强烈地去乙酰化，对HBD furin切割区域的K220具有中等活性，对K211和K212具有高活性。这些乙酰化位点以前没有报道过，可能是由于肽独特的亲水性。总的来说，我们的研究结果表明，sirtuin导向的SOD3去乙酰化恢复了furin的裂解，定义了氧化还原稳态和乙酰化导向的细胞外氧化应激代谢调节之间的重要联系。

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引用次数: 0

Regulation of P450-derived epoxy fatty acids in cardiovascular diseases p450衍生环氧脂肪酸在心血管疾病中的调节作用

Redox Biochemistry and Chemistry

Pub Date : 2025-10-13 DOI: 10.1016/j.rbc.2025.100064

Matthew L. Edin, Joan P. Graves, Darryl C. Zeldin

The cytochrome P450 (P450 or CYP) superfamily, while extensively recognized for xenobiotic metabolism, is also critically involved in the biosynthesis of lipid mediators from polyunsaturated fatty acids (PUFAs). Distinct from cyclooxygenase (COX) and lipoxygenase (LOX) pathways, P450 enzymes uniquely catalyze the metabolism of PUFAs such as arachidonic acid (AA), to epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) and mid-chain or ω-terminal hydroxyeicosatrienoic acids (HETEs). Eicosanoid biosynthesis is initiated by phospholipase A₂ (PLA₂)-mediated release of PUFAs from cellular membranes. Members of the CYP1-CYP4 subfamilies, including prominent human isoforms like CYP2C8, CYP2C9, and CYP2J2, exhibit significant epoxygenase activity, yielding regio- and stereo-specific EETs. These P450-derived oxylipins exert diverse physiological effects, influencing critical processes such as vascular tone, inflammation, angiogenesis, and ischemia-reperfusion injury. Their biological actions are often modulated by soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH), which hydrolyze EETs to less active dihydroxyeicosatrienoic acids (DHETs). Furthermore, P450s metabolize other PUFAs, including linoleic acid (LA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), generating distinct EpFAs with varying biological effects. Understanding the complex interplay of P450 isoforms, their substrate preferences, and the subsequent metabolic fates of their products is crucial for elucidating their functional roles in health and disease.

细胞色素P450 （P450或CYP）超家族被广泛认为与异种代谢有关，同时也参与了多不饱和脂肪酸（PUFAs）的脂质介质的生物合成。与环氧合酶（COX）和脂氧合酶（LOX）途径不同，P450酶独特地催化花生四烯酸（AA）等pufa代谢为环氧脂肪酸（epfa），如环氧二十碳三烯酸（EETs）和中链或ω-末端羟基二十碳三烯酸（HETEs）。类二十烷酸的生物合成是由磷脂酶A2 （PLA2）介导的PUFAs从细胞膜释放而启动的。CYP1-CYP4亚家族的成员，包括CYP2C8、CYP2C9和CYP2J2等重要的人类亚型，表现出显著的环氧合酶活性，产生区域特异性和立体特异性eet。这些p450衍生的氧化脂具有多种生理作用，影响血管张力、炎症、血管生成和缺血再灌注损伤等关键过程。它们的生物作用通常由可溶性环氧化物水解酶（sEH）和微粒体环氧化物水解酶（mEH）调节，后者将eet水解成活性较低的二羟基二碳三烯酸（DHETs）。此外，p450还代谢亚油酸（LA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）等pufa，生成不同的epfa，并具有不同的生物学效应。了解P450异构体的复杂相互作用，它们的底物偏好，以及它们的产物的后续代谢命运，对于阐明它们在健康和疾病中的功能作用至关重要。

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引用次数: 0