reactive oxygen species (ROS)

活性氧 (ROS)
  • 文章类型: Journal Article
    最近,许多研究已经证实了壳聚糖纳米颗粒(CNP)作为一种可行的药物递送载体对于提高抗癌药物在癌症治疗中的功效的重要性。它是一种高分子和天然生物聚合物化合物,使用起来比金属纳米粒子更稳定、更安全。蜂毒(BV),一种防御毒液,已被证明具有抗肿瘤作用,神经保护,抗炎,镇痛药,和抗感染特性。此外,细胞死亡的调节与活性氧(ROS)介导的细胞凋亡有关,通过氧化应激事件诱导线粒体损伤和内质网应激。因此,这项研究旨在说明ROS介导的对CNP负载的BV(CNP-BV)治疗癌细胞的作用,并解释了ROS产生对线粒体和ER的不利影响。我们发现靶向CNP-BV通过诱导大量ROS产生对MCF-7(IC50437.2μg/mL)和HepG2(IC50109.5μg/mL)具有很高的细胞毒性,这又导致激活线粒体级联和内质网应激。这些结果强调了ROS产生在诱导癌细胞凋亡中的作用。
    Recently, numerous studies have confirmed the importance of chitosan nanoparticles (CNP) as a viable drug delivery carrier for increasing the efficacy of anticancer drugs in cancer treatment. It is a macromolecule and natural biopolymer compound, more stable and safer in use than metal nanoparticles. Bee venom (BV), a form of defense venom, has been shown to have anti-tumor, neuroprotective, anti-inflammatory, analgesic, and anti-infectivity properties. Moreover, the regulation of cell death has been linked to reactive oxygen species (ROS)-mediated cell apoptosis, which induces mitochondrial damage and ER stress through oxidative stress events. Therefore, this study aimed to illustrate the ROS-mediated effect on the cancer cells treatment with CNP-loaded BV (CNP-BV) and explained the adverse effects of ROS generation on Mitochondria and ER. We have found that the targeted CNP-BV were high in cytotoxicity against MCF-7 (IC50 437.2 μg/mL) and HepG2 (IC50 109.5 μg/mL) through the induction of massive generation of ROS, which in turn results in activating the mitochondrial cascade and ER stress. These results highlighted the role of ROS generation in inducing apoptosis in cancer cells.
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  • 文章类型: Journal Article
    准确和早期发现动脉粥样硬化(AS)对于有效治疗至关重要。然而,用于有效诊断AS的荧光探针经常遇到深度组织渗透不足,这阻碍了对斑块易损性的可靠评估。在这项工作中,活性氧(ROS)激活的近红外(NIR)荧光和光声(FL/PA)双模型探针TPA-QO-B是通过偶联两个发色团(TPA-QI和O-OH)和ROS-特异性基团苯基硼酸酯而开发的。ROS特异性基团的掺入不仅诱导吸光度的蓝移,但也抑制了TPA-QO-OH的ICT过程,产生可忽略的初始FL/PA信号。ROS触发TPA-QO-B转化为TPA-QO-OH,导致FL/PA信号的同时放大。TPA-QO-B对ROS的特殊选择性使其有效地将AS小鼠与健康小鼠区分开。NIR发射可以实现0.3cm的组织穿透成像深度。此外,其PA775信号具有穿透高达0.8厘米厚度的组织的能力,确保AS模型小鼠早期的体内成像。ROS触发的FL/PA双信号放大策略提高了准确性,同时解决了深层组织穿透问题,为生命科学和临床前应用中的体内生物标志物跟踪提供了一个有前途的工具。
    Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.
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  • 文章类型: Journal Article
    已合成了两种经叔丁基磺酰基四外围取代并配位锌(II)或铂(II)离子的酞菁衍生物,随后对其光学和光化学性质进行了研究。以及细胞中的生物活性,组织工程,和动物模型。我们的研究表明,两种合成的酞菁都是活性氧(ROS)的有效发生器。PtSO2tBu表现出优异的产生单线态氧的能力(ΦΔ=0.87-0.99),而ZnSO2tBu除了1O2(ΦΔ=0.45-0.48)外还能有效地产生其他ROS,特别是·OH。考虑到未来的生物医学应用,还确定了测试的酞菁对生物膜的亲和力(分配系数;logPow)及其与血清白蛋白的主要相互作用。为了方便他们的生物管理,使用Pluronic三嵌段共聚物开发了这些酞菁的水分散性制剂,以防止自聚集并改善它们向癌细胞和组织的递送。结果表明,当将酞菁掺入可定制的聚合物胶束中时,细胞摄取和光毒性显着增加。此外,在hiPSC递送的类器官和携带CT26肿瘤的BALB/c小鼠中研究了包封的酞菁在体内的分布和光动力学功效的改善.两种光敏剂均表现出强的抗肿瘤活性。值得注意的是,血管靶向光动力疗法(V-PDT)导致84%的ZnSO2tBu和100%的PtSO2tBu治疗的小鼠完全根除肿瘤,到目前为止,在治疗后的五个月内没有观察到复发。在PtSO2tBu的情况下,效果明显更强,提供更广泛的光剂量适合实现有效的PDT。
    Two phthalocyanine derivatives tetra-peripherally substituted with tert-butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO2tBu demonstrated an outstanding ability to generate singlet oxygen (ΦΔ = 0.87-0.99), while ZnSO2tBu in addition to 1O2 (ΦΔ = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log Pow) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of ZnSO2tBu and 100% of PtSO2tBu-treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO2tBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.
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  • 文章类型: Journal Article
    呼吸性爆发氧化酶同源物(RBOHs)参与植物生长,发展,和压力适应。OsRBOHs如何影响根毛形成,从而影响水稻的养分获取和抗旱性尚不清楚。我们敲除了水稻中在根中表达的六个OsRBOH基因,并确定OsRBOHE是唯一影响根毛形成的基因。OsRBOHE在根表皮中强烈表达,根毛和分茎芽。OsRBOHE位于质膜。OsRBOHE的敲除减少了根毛和分till芽中活性氧的产生,涉及细胞壁生物发生的下调基因,根毛长度和分till率减少了90%和30%,分别。OsRBOHE的敲除仅在有氧条件下低有效磷土壤中降低了磷的获取,但在高磷土壤或洪水泛滥的条件下,磷可能不受扩散限制。基因敲除OsRBOHE对根毛形成和相关根鞘的影响显着降低了水稻的抗旱性。一起来看,OsRBOHE对于根毛的形成和分till以及水稻的抗旱至关重要。根毛对水稻磷吸收的贡献仅限于需氧土壤。
    Respiratory Burst Oxidase Homologues (RBOHs) are involved in plant growth, development, and stress adaptation. How OsRBOHs affect root hair formation and consequently nutrient acquisition and drought resistance in rice is not well understood. We knocked out six OsRBOH genes in rice that were expressed in roots and identified OsRBOHE as the only one affecting root hair formation. OsRBOHE was strongly expressed in the root epidermis, root hairs and tiller buds. OsRBOHE is localised at the plasma membrane. Knockout of OsRBOHE decreased reactive oxygen species generation in the root hairs and tiller buds, downregulated genes involved in cell wall biogenesis, and decreased root hair length and tillering by 90% and 30%, respectively. Knockout of OsRBOHE decreased phosphorus acquisition only in low available P soil under aerobic conditions, but not in high P soil or under flooded conditions when P was likely not limited by diffusion. Knockout of OsRBOHE markedly decreased drought resistance of rice plants through the effect on root hair formation and the associated rhizosheath. Taken together, OsRBOHE is crucial for root hair formation and tillering and consequently on drought resistance in rice. The contribution of root hairs to P acquisition in rice is limited to aerobic soil.
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  • 文章类型: Journal Article
    这篇综述总结了有关氧化修饰的低密度脂蛋白(LDL)在动脉粥样硬化和糖尿病发生中的作用的长期实验研究和文献数据。研究表明,没有“氧化”(含脂过氧化物)LDL,但是二羰基修饰的LDL是动脉粥样硬化的(在清道夫受体的帮助下被培养的巨噬细胞主动捕获),也引起凝集素样氧化低密度脂蛋白受体1(LOX-1)和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶1(NOX-1)基因在内皮细胞中的表达,刺激细胞凋亡和内皮功能障碍。获得的数据使我们能够证明动脉粥样硬化和糖尿病的药物治疗新方法。
    This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not \"oxidized\" (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.
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  • 文章类型: Journal Article
    放大氧化应激以破坏细胞内氧化还原稳态可以加速肿瘤细胞死亡。在这项工作中,氧化应激放大器(PP@T)用于增强肿瘤氧化治疗以减少肿瘤生长和转移。通过将MTH1抑制剂(TH588)嵌入PDA包覆的卟啉金属有机框架PCN-224中,已成功构建了纳米放大器。从孔隙中可控制释放的TH588可以通过防止8-oxo-dG的水解来阻碍MTH1介导的损伤修复过程,从而放大了超声照射下PP@T的声动力治疗所引起的氧化应激并加剧了DNA的氧化损伤。此外,PP@T能有效诱导免疫原性细胞死亡,引发全身抗肿瘤免疫反应。当与免疫检查点阻断联合给药时,PP@T不仅阻碍了原发肿瘤的进展,而且在乳腺癌小鼠模型中实现了明显的抗转移,包括原位和人工全身转移模型。此外,纳米平台还提供了用于体内治疗指导的光声成像。总之,通过放大氧化应激和活性氧敏化的免疫治疗,这种图像引导的纳米系统显示出高度特异性的潜力,针对肿瘤细胞的有效联合治疗,对正常细胞的副作用可忽略不计,这将为精确的肿瘤治疗提供新的见解。
    Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano-amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA-coated porphyrin metal-organic framework PCN-224. The controllable-released TH588 is demonstrated from pores can hinder MTH1-mediated damage-repairing process by preventing the hydrolysis of 8-oxo-dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole-body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image-guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side-effects to normal cells which will provide a new insight for precise tumor treatment.
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  • 文章类型: Journal Article
    脂质重塑对于各种细胞活动和植物的胁迫耐受性至关重要;然而,关于重金属镉(Cd)诱导的脂质动力学知之甚少。在这项研究中,我们调查了Cd暴露下水稻(Oryzasativa)中的磷脂谱。我们观察到磷脂酰胆碱和磷脂酰丝氨酸的总量显着下降,与Cd胁迫引起的磷脂酸(PA)升高形成鲜明对比。此外,Cd胁迫促使磷脂酶D(PLD)活化,诱导PLDα1表达。OsPLDα1敲除突变体(Ospldα1)对Cd的敏感性增强,其特征在于Cd处理后根部过氧化氢的积累增加和PA的产生减少。相反,PLDα1过表达(OsPLDα1-OE)系表现出对Cd的耐受性增强,抑制呼吸爆发氧化酶同源物(Rboh)基因的转录。相对于野生型,Ospldα1和OsPLDα1-OE植物中与Cd吸收和转运相关的基因的转录水平得到了相应的调节。一起来看,我们的发现强调了OsPLDα1通过调节水稻的活性氧稳态和脂质重塑在赋予Cd耐受性中的关键作用。
    Lipid remodeling is crucial for various cellular activities and the stress tolerance of plants; however, little is known about the lipid dynamics induced by the heavy metal cadmium (Cd). In this study, we investigated the phospholipid profiles in rice (Oryza sativa) under Cd exposure. We observed a significant decline in the total amounts of phosphatidylcholine and phosphatidylserine, contrasted with an elevation in phosphatidic acid (PA) due to Cd stress. Additionally, Cd stress prompted the activation of phospholipase D (PLD) and induced the expression of PLDα1. OsPLDα1 knockout mutants (Ospldα1) showed increased sensitivity to Cd, characterized by a heightened accumulation of hydrogen peroxide in roots and diminished PA production following Cd treatment. Conversely, PLDα1-overexpressing (OsPLDα1-OE) lines demonstrated enhanced tolerance to Cd, with suppressed transcription of the respiratory burst oxidase homolog (Rboh) genes. The transcription levels of genes associated with Cd uptake and transport were accordingly modulated in Ospldα1 and OsPLDα1-OE plants relative to the wild-type. Taken together, our findings underscore the pivotal role of OsPLDα1 in conferring tolerance to Cd by modulating reactive oxygen species homeostasis and lipid remodeling in rice.
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  • 文章类型: Journal Article
    新的抗癌策略通过提高癌细胞的致死能力来减少对健康组织的副作用。开发具有良好生物利用度和选择性的有效颗粒仍然存在问题。对于不良特征,绿色化学被用来合成最好的化合物,或天然颗粒得到改善。光动力疗法(PDT),以酞菁(PC)为模型,仍然提供第二代敏化剂,它们补充有金属离子,如Zn2+,Al3+,或Ga3+。氢氧化八羧基酞菁镓(Ga(OH)PcOC),是为治疗皮肤癌而设计的,并被用作正常皮肤细胞系的促凋亡和促氧化剂,成纤维细胞(NHDF),和角质形成细胞(HaCaT),在体外具有对黑色素瘤癌细胞(Me45)的有希望的选择性。与以前报道的发现相比,ZnPcOC以较高的剂量作用于皮肤细胞系,对Ga(OH)PcOC的敏感性允许敏化剂剂量的有效降低。有效剂量,对于一种新型Ga(OH)PcOC颗粒,在Me45癌细胞上从30µM显着降低到6µM,使用24小时MTT活力测试,以及细胞计数促氧化和促凋亡测定。在没有活性氧(ROS)升高或凋亡诱导的情况下,有前途的光敏剂不会降低正常成纤维细胞和角质形成细胞的活力。对先前发现的改进是基于Ga的光敏剂对癌症Me45细胞的选择性更好,然后在Zn基化合物中观察到。
    Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn2+, Al3+, or Ga3+. Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds.
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  • 文章类型: Journal Article
    生物肥料是环境友好的化合物,可以促进植物生长并替代化学合成的产品。在这项研究中,一种新的velezensis芽孢杆菌菌株,指定JZ,从草莓植物的根中分离出,并对引起草莓叶斑病的病原体altitudinism-1表现出有效的拮抗特性。JZ的发酵液对该病原体的抑制率为47.43%。使用优化的酸沉淀法,从JZ发酵液中获得脂肽的粗提物。VelezensisJZ发酵液的粗提物并未显着破坏B.alitdinism-1的细胞通透性,而显着降低了细胞膜上的Ca2-ATPase活性,并显着提高了细胞内活性氧(ROS)浓度。为了鉴定粗提物中的活性化合物,采用QTOF-MS/MS,揭示了四种抗菌化合物:芬霉素,iturin,surfactin,和一种被称为杆菌烯的多烯抗生素。菌株JZ还产生了各种植物生长促进物质,如蛋白酶,IAA,和铁载体,这有助于植物在病原体感染下生存。这些发现表明,JZ菌株作为针对B.altitudinis的生物防治剂具有重要的潜力,为植物细菌性疾病的管理提供了有希望的途径。
    Biofertilizers are environmentally friendly compounds that can enhance plant growth and substitute for chemically synthesized products. In this research, a new strain of the bacterium Bacillus velezensis, designated JZ, was isolated from the roots of strawberry plants and exhibited potent antagonistic properties against Bacillus altitudinis m-1, a pathogen responsible for leaf spot disease in strawberry. The fermentation broth of JZ exerted an inhibition rate of 47.43% against this pathogen. Using an optimized acid precipitation method, crude extracts of lipopeptides from the JZ fermentation broth were obtained. The crude extract of B. velezensis JZ fermentation broth did not significantly disrupt the cell permeability of B. altitudinis m-1, whereas it notably reduced the Ca2+-ATPase activity on the cell membrane and markedly elevated the intracellular reactive oxygen species (ROS) concentration. To identify the active compounds within the crude extract, QTOF-MS/MS was employed, revealing four antimicrobial compounds: fengycin, iturin, surfactin, and a polyene antibiotic known as bacillaene. The strain JZ also produced various plant-growth-promoting substances, such as protease, IAA, and siderophore, which assists plants to survive under pathogen infection. These findings suggest that the JZ strain holds significant potential as a biological control agent against B. altitudinis, providing a promising avenue for the management of plant bacterial disease.
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  • 文章类型: Journal Article
    由于线粒体功能障碍,皮肤老化与线粒体活性氧(mtROS)的产生增加有关,各种植物营养素和雌激素已被证明可以改善皮肤健康。因此,本研究的目的是研究化学诱导的线粒体功能障碍对真皮成纤维细胞的损害,并研究类胡萝卜素的保护作用机制,多酚,和雌二醇。鱼藤酮,复合物I抑制剂,导致人真皮成纤维细胞线粒体功能障碍,显著降低呼吸和ATP水平,其次是线粒体和胞质ROS增加,导致细胞凋亡,衰老细胞数量的增加,基质金属蛋白酶-1(MMP1)分泌增加,胶原蛋白分泌减少。用富含类胡萝卜素的番茄提取物预处理,迷迭香提取物,雌二醇逆转了这些作用。这些保护作用可以部分解释为抗氧化反应元件(ARE/Nrf2)转录活性的协同激活由保护性化合物和鱼藤酮,这导致了抗氧化蛋白如NQO1的上调。为了确定ARE/Nrf2活性是否对细胞保护至关重要,我们使用Nrf2抑制剂ML385和曲霉毒素A对其进行抑制。这种抑制通过降低测试化合物减少细胞溶质ROS的作用而显著降低了测试化合物的保护作用。我们的研究结果表明,植物营养素和雌二醇保护皮肤细胞免受mtROS引起的损伤,因此可以延缓皮肤细胞衰老,改善皮肤健康。
    Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal fibroblasts by chemically induced mitochondrial dysfunction and to study the mechanism of the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a Complex I inhibitor, caused mitochondrial dysfunction in human dermal fibroblasts, substantially reducing respiration and ATP levels, followed by increased mitochondrial and cytosolic ROS, which resulted in apoptotic cell death, an increased number of senescent cells, increased matrix metalloproteinase-1 (MMP1) secretion, and decreased collagen secretion. Pre-treatment with carotenoid-rich tomato extracts, rosemary extract, and estradiol reversed these effects. These protective effects can be partially explained by a cooperative activation of antioxidant response element (ARE/Nrf2) transcriptional activity by the protective compounds and rotenone, which led to the upregulation of antioxidant proteins such as NQO1. To determine if ARE/Nrf2 activity is crucial for cell protection, we inhibited it using the Nrf2 inhibitors ML385 and ochratoxin A. This inhibition markedly reduced the protective effects of the test compounds by diminishing their effect to reduce cytosolic ROS. Our study results indicate that phytonutrients and estradiol protect skin cells from damage caused by mtROS, and thus may delay skin cell senescence and improve skin health.
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