过氧化氢酶在植物胁迫响应中的功能研究进展

作为信号分子的过氧化氢是植物复杂信号传导中的一个重要组成部分,它介导了多种植物胁迫反应并对其平衡的维持和调控起到了非常重要的作用。越来越多的研究证实了胁迫反应中过氧化氢酶与过氧化氢含量的变化有一定的关系,同时又和其它信号因子存在着交互作用。本文综述了近年来过氧化氢酶在植物遭受病害、水分、盐渍、光等胁迫反应中的调控作用,以及在这些反应中过氧化氢酶、过氧化氢、蛋白激酶、转录因子与其它信号分子所构成的可能信号网络和过氧化氢的限速步骤方面的研究进展。     

NADPH氧化酶与ROS信号区域化

最近有关活性氧物质 (ROS)的研究取得了突飞猛进的进展,尤其是其作为第二信使介导了许多生理性与病理性细胞事件,包括细胞分化、过度生长、增殖及凋亡.为了避免ROS的毒性产生特异性的信号转导,ROS的产生与代谢必须被严格调控;其具体的调控机制一直是人们关注的焦点. 最近有关ROS区域化观点的提出解决了这一问题. NADPH是生成ROS的主要来源. 研究发现,NADPH氧化酶及其衍生的ROS存在于机体的多种组织内,且在细胞中呈区域化分布,对细胞内信号的精确调控具有至关重要的作用. NADPH一方面通过小窝/脂筏组装成功能型复合物,从而产生ROS区域化;另一方面,NADPH通过其不同亚细胞定位亚基与各种靶蛋白之间的相互作用,产生ROS特异性. 本文系统综述了NADPH衍生的ROS信号区域化,为进一步理解ROS信号在各种生理或病理过程的分子调控机制提供理论依据.     

靶向调控Nrf2-ARE通路的miRNAs研究进展

活性氧类(reactive oxygen species,ROS)在体内产生与清除的失衡,往往是导致机体病变的重要因素。研究表明,多条信号通路参与调节机体内ROS的平衡,其中核因子E2相关因子2-抗氧化反应元件(nuclear factor erythroid 2 related factor 2-antioxidant responsive element,Nrf2-ARE)通路活化,能诱导抗氧化酶表达,从而清除过量的活性氧,发挥细胞保护作用。Nrf2-ARE通路是当前研究的热点通路之一,阐明该通路活化或失活的分子机制亦是目前研究的重点。微RNA(microRNAs,miRNAs)是真核生物中广泛存在的能调节基因表达的一类非编码、极短小RNA分子,目前已发现多种miRNAs可作用于Nrf2-ARE信号通路上的重要分子,调控其表达,进而参与调控信号通路的活化与失活,在维持机体氧化还原稳态中扮演重要角色。现就近年来参与调控Nrf2-ARE通路的miRNAs的研究进展做一综述,以期为进一步阐明该通路在维持机体氧化反应稳态中的作用提供帮助。     

p53参与代谢调控的研究进展

p53作为肿瘤抑制因子,其不仅参与遗传毒性应激调节,而且在代谢平衡调控中也发挥重要作用。当机体或细胞处于不同生理逆境时,活化的p53通过参与糖代谢、脂肪酸代谢、ROS水平等相关调节信号通路影响各种代谢途径,进而通过诱导细胞周期阻滞、修复、衰老或凋亡的发生,最终调控机体或细胞产生代谢应激。总结了近年来p53途径的相关报道,对p53与癌症、代谢综合证的关系进行了阐述,以期为进一步理解p53参与的代谢调控提供参考。     

支链氨基酸代谢及其与疾病的关系

亮氨酸、异亮氨酸和缬氨酸的疏水侧链都具有分支的甲基基团，因而被统称为支链氨基酸(branched chain amino acids, BCAAs)。作为机体的必需氨基酸，除了作为蛋白质合成的基本原料，BCAAs及其各种分解代谢产物还可以作为信号分子，调控从蛋白质合成到胰岛素分泌等众多生理过程。因此，它们的正常代谢对机体生命活动至关重要。越来越多的证据表明，BCAAs代谢异常与多种疾病关系密切，包括枫糖尿病、神经系统疾病、糖尿病、心血管疾病、肝疾病和癌症等。本文详细概述了哺乳动物中BCAAs分解代谢的基本模式、调控机制(主要关注对2个关键代谢酶BCAT和BCKDH的调控)以及BCAAs参与mTOR和AMPK信号通路在机体代谢中发挥的作用。总结了BCAAs代谢异常与多种疾病的关系，并对有关的矛盾观点进行阐述和解释。近年来，BCAAs代谢及调控在疾病发生发展中的作用成为研究热点，为相关疾病预防和治疗提供了新视角。本综述将为进一步研究提供线索。     

ROS信号对植物抗性的调控作用研究进展

活性氧(reactive oxygen species,ROS)是植物体代谢所产生的小分子化合物,既是生长发育和防御途径的关键调节因子,又是需氧代谢的有毒副产物。植物细胞的生理过程受一个被活性氧调节的氧化还原网状途径的调控,本文从植物体内ROS产生的部位与时空特异性、ROS信号与NO和Ca2+波信号的互作等方面综述了ROS信号对植物抗性的调控作用研究进展。     

信号分子ppGpp与微生物环境适应性

微生物能感知环境胁迫信号,通过触发严谨反应对生长速率进行调节,并通过一系列代谢调控,使细胞能在不利环境中生存。高度磷酸化的鸟苷四/五磷酸ppGpp/pppGpp（文中以ppGpp统称）作为信号分子对微生物生理具有广泛的调节作用,至今仍是微生物学研究热点之一。ppGpp对于微生物适应高温、高压等环境起到了积极的作用。综述了信号分子ppGpp合成降解机制及其调控微生物适应性方面的研究进展。     

植物中参与活性氧调控的基因网络

植物体内活性氧（reactive oxygen species,ROS）是氧化还原反应的必然副产物,具极高的活性和毒性,从而对细胞产生毒害。同时,活性氧作为信号分子对很多生理过程诸如植物生长发育、细胞程序化死亡及生物和非生物胁迫应答起调控作用。植物中ROS双重作用的协调机制目前尚不明确,确定的是细胞中ROS维持于稳定水平需要精细的调节。拟南芥中至少包括152个基因组成的网络参与ROS的调控,该网络具高度的灵活性和互补性。本文综述了ROS网络中鉴定的一些关键基因及细胞学定位和协同作用,ROS信号转导,尤其是叶绿体中ROS信号的调控。     

抗病毒免疫中干扰素与炎症信号通路的交互调控：防御反应与维持稳态

天然免疫是机体通过识别自身或外部危险信号后,为维持体内稳态而逐步建立起来的一系列防御反应,当宿主细胞内的模式识别受体识别胞内病原相关分子模式后激活干扰素(interferon, IFN)、核因子-kappa B (nuclear factor-kappa B, NF-κB)和炎性小体等信号通路。IFNs在天然免疫应答中发挥重要作用,它诱导的抗病毒基因能够通过多种方式抵御病毒的感染,炎症反应则是机体自动的防御反应,能够在病毒感染机体时释放促炎性细胞因子以调控机体的免疫反应,进而发挥抗病毒作用。在病毒感染过程中,IFN信号通路与炎症反应调控网络中的关键分子如NF-κB/RelA、PKR等存在一定的交互作用,此外,IFN信号通路及其产生的细胞因子又影响其他信号通路的活化,进而调控机体的免疫应答以维持自身稳态,它们之间的交互调控失衡将会引起过度炎症反应,导致组织器官的免疫病理损伤,例如SARS-CoV-2感染机体时产生的过度炎症反应。本文综述了机体抗病毒免疫过程中干扰素信号通路与炎症反应之间的交互调控,为研发抗病毒策略提供新思路。     

BAK1调控植物免疫信号识别和转导的分子机制

植物通过类受体激酶感知环境变化,产生相应的信号来调控机体生长发育。BAK1 (BRI1-associated kinase 1)是其中研究最深入的类受体激酶之一。它调控多种生理过程的信号转导,如植物生长发育、细胞死亡和植物免疫等。本文综述了BAK1作为模式识别受体的共受体以及信号转导的调控子,调控免疫信号识别和转导的机理。以期为深入研究BAK1基因家族在植物抗病反应中的作用,阐明植物免疫信号转导途径提供信息。     

SK-N-MC Cell Death Occurs by Distinct Molecular Mechanisms in Response to Hydrogen Peroxide and Superoxide Anions: Involvements of JAK2-STAT3, JNK, and p38 MAP Kinases Pathways

Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Nerve cells are incessantly exposed to environmental stresses leading to overproduction of some harmful species like reactive oxygen species (ROS). ROS including hydrogen peroxide and superoxide anion are potent inducers of various signaling pathways encompassing MAPKs and JAK-STAT pathways. In the current study, we scrutinized the effects of hydrogen peroxide and/or menadione (superoxide anion generator) on JNK/p38-MAPKs and JAK2-STAT3 pathways to elucidate the mechanism(s) by which each oxidant modulated the above-mentioned pathways leading to SK-N-MC cell death. Our results delineated that hydrogen peroxide and superoxide anion radical induced distinct responses as we showed that STAT3 and p38 were activated in response to hydrogen peroxide, but not superoxide anion radicals indicating the specificity in ROS-induced signaling pathways activations and behaviors. We also observed that menadione induced JNK-dependent p53 expression and apoptotic death in SK-N-MC cells while H₂O₂-induced JNK activation was p53 independent. Thus, we declare that ROS type has a key role in selective instigation of JNK/p38-MAPKs and JAK2-STAT3 pathways in SK-N-MC cells. Identifying these differential behaviors and mechanisms of hydrogen peroxide and superoxide anion functions illuminates the possible therapeutic targets in the prevention or treatment of ROS-induced neurodegenerative diseases such as Alzheimer’s disease.     

植物细胞活性氧种类、代谢及其信号转导

越来越明显的证据表明,植物体十分活跃的产生着活性氧并将之作为信号分子、进而控制着诸如细胞程序性死亡、非生物胁迫响应、病原体防御和系统信号等生命过程,而不仅是传统意义上的活性氧是有氧代谢的附产物。日益增多的证据显示,由脱落酸、水杨酸、茉莉酸与乙烯以及活性氧所调节的激素信号途径,在生物和非生物胁迫信号的“交谈”中起重要作用。活性氧最初被认为是动物吞噬细胞在宿主防御反应时所释放的附产物,现在的研究清楚的表明,活性氧在动物和植物细胞信号途径中均起作用。活性氧可以诱导细胞程序性死亡或坏死、可以诱导或抑制许多基因的表达,也可以激活上述级联信号。近来生物化学与遗传学研究证实过氧化氢是介导植物生物胁迫与非生物胁迫的信号分子,过氧化氢的合成与作用似乎与一氧化氮有关系。过氧化氢所调节的下游信号包括钙“动员”、蛋白磷酸化和基因表达等。     

Reactive oxygen species as cardiovascular mediators: Lessons from endothelial-specific protein overexpression mouse models

The term reactive oxygen species (ROS) summarizes several small chemical compounds such as superoxide, peroxynitrite, hydrogen peroxide and nitric oxide. The stoichiometry of the chemical reactions underlying generation and metabolism is subject of tight enzymatic regulation resulting in well balanced steady-state concentrations throughout the healthy body. ROS are short-lived and usually active at the site of production only, e.g. in vascular endothelial cells. Although an increase of vascular ROS-production is considered an important pathogenic factor in cardiovascular diseases, there is evidence for physiological or even beneficial effects as well. We have generated several transgenic mice using the Tie-2 promotor which expresses an enzyme of interest specifically in vascular endothelial cells. Here, we review some results obtained with mice carrying a Tie-2-driven overexpression of catalase or endothelial nitric oxide synthase (eNOS). Tie-2-catalase mice have a strongly reduced steady-state concentration of vascular hydrogen peroxide and show profound hypotension that is not dependent on the bioavailability of endothelial nitric oxide but is completely reversible by treatment with the catalase inhibitor aminotriazole. A similar hypotension was observed in transgenic mice with an endothelial-specific overexpression of eNOS but this hypotension is entirely dependent on vascular eNOS activity. These observations suggest a tonic effect of hydrogen peroxide on vascular smooth muscle. Further studies suggested that hydrogen peroxide promotes the exercise-induced increase of vascular eNOS expression and inhibits the release of endothelial progenitor cells induced by exercise training. In summary, our data support the concept of a dual role of ROS in the vascular system.     

Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay)

Reactive oxygen species (ROS) are produced by a wide variety of chemicals and physiological processes in which enzymes catalyse the transfer of electrons from a substrate to molecular oxygen. The immediate products of such reactions, superoxide anion radicals and hydrogen peroxide can be metabolised by enzymes such as superoxide dismutase (SOD) and catalase (CAT), respectively, and depending on its concentration by Vitamin C (Vit C). Under certain circumstances the ROS form highly reactive hydroxyl radicals. We examined human sperm and lymphocytes after treatment with six oestrogenic compounds in the Comet assay, which measures DNA damage, and observed that all caused damage in both cell types. The damage was diminished in nearly all cases by catalase, and in some instances by SOD and Vit C. This response pattern was also seen with hydrogen peroxide. This similarity suggests that the oestrogen-mediated effects could be acting via the production of hydrogen peroxide since catalase always markedly reduced the response. The variable responses with SOD indicate a lesser involvement of superoxide anion radicals due to SOD-mediated conversion of superoxide to hydrogen peroxide generally causing a lower level of DNA damage than other ROS. The variable Vit C responses are explained by a reduction of hydrogen peroxide at low Vit C concentrations and a pro-oxidant activity at higher concentrations. Together these data provide evidence that inappropriate exposure to oestrogenic compounds could lead to free-radical mediated damage. It is believed that the observed activities were not generated by cell free cell culture conditions because increased responses were observed over and above control values when the compounds were added, and also increasing dose-response relationships have been found after treatment with such oestrogenic compounds in previously reported studies.     

A ratiometric and two-photon fluorescent probe for imaging hydrogen peroxide in living cells

As an important reactive oxygen species (ROS), hydrogen peroxide plays a significant role in the life activity system, and its abnormal levels are closely related to many diseases. Developing effective fluorescent probes for detecting hydrogen peroxide is very urgent. Therefore, we constructed a probe Z that can detect hydrogen peroxide in ratio. It has naphthimide as the fluorophore and phenylboronic acid pinacol esters as the recognition group. It shows higher sensitivity, lower detection limit, higher selectivity, and broad pH applicability. Moreover, probe Z has low cytotoxicity that can be used to detect exogenous hydrogen peroxide in HeLa cells and might be a potential tool for studying hydrogen peroxide in physiological activities.     

Hydrogen peroxide: a Jekyll and Hyde signalling molecule

Reactive oxygen species (ROS) are a group of molecules produced in the cell through metabolism of oxygen. Endogenous ROS such as hydrogen peroxide (H₂O₂) have long been recognised as destructive molecules. The well-established roles they have in the phagosome and genomic instability has led to the characterisation of these molecules as non-specific agents of destruction. Interestingly, there is a growing body of literature suggesting a less sinister role for this Jekyll and Hyde molecule. It is now evident that at lower physiological levels, H₂O₂ can act as a classical intracellular signalling molecule regulating kinase-driven pathways. The newly discovered biological functions attributed to ROS include proliferation, migration, anoikis, survival and autophagy. Furthermore, recent advances in detection and quantification of ROS-family members have revealed that the diverse functions of ROS can be determined by the subcellular source, location and duration of these molecules within the cell. In light of this confounding paradox, we will examine the factors and circumstances that determine whether H₂O₂ acts in a pro-survival or deleterious manner.     

ABA,ROS and NO are Key Players During Switchgrass Seed Germination

Seed dormancy and germination are complex physiological processes usually under hormonal control. Germination of seeds from many plants including switchgrass, are inhibited by ABA and promoted by NO or ROS. However, ABA apparently requires both ROS and NO as intermediates in its action, with ROS produced by membrane-bound NADPH-oxidases responsive to ABA. In switchgrass seeds, externally supplied hydrogen peroxide (ROS), but not NO will overcome ABA-imposed inhibition of germination. Stimulation of germination by external ROS can be partially blocked by NO-scavengers, suggesting that NO is required for seed germination in switchgrass as well as for ABA-induced inhibition of germination. Collectively, these data suggest that multiple mechanisms might be required to sense and respond to varying levels of ABA, NO and ROS in switchgrass seeds.Key Words: switchgrass, seed germination, ROS, hydrogen peroxide, ABA, nitric oxide     

In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice

In mtDNA mutator mice, mtDNA mutations accumulate leading to a rapidly aging phenotype. However, there is little evidence of oxidative damage to tissues, and when analyzed ex vivo, no change in production of the reactive oxygen species (ROS) superoxide and hydrogen peroxide by mitochondria has been reported, undermining the mitochondrial oxidative damage theory of aging. Paradoxically, interventions that decrease mitochondrial ROS levels in vivo delay onset of aging. To reconcile these findings, we used the mitochondria‐targeted mass spectrometry probe MitoB to measure hydrogen peroxide within mitochondria of living mice. Mitochondrial hydrogen peroxide was the same in young mutator and control mice, but as the mutator mice aged, hydrogen peroxide increased. This suggests that the prolonged presence of mtDNA mutations in vivo increases hydrogen peroxide that contributes to an accelerated aging phenotype, perhaps through the activation of pro‐apoptotic and pro‐inflammatory redox signaling pathways.     

Rapid suppression of multidrug resistance of leukemic cells by oxidative srtess

The effect of a short-time (1 h) oxidative stress on multidrug resistance (MDR) of murine leukemic P388VR cells has been investigated. We studied the production of reactive oxygen species (ROS) in cells depending on the composition of medium and the concentration of cells and hydrogen peroxide, as well as the effect of hydrogen peroxide on MDR of cells. MDR was determined from the transport of calcein acetoxymethyl ester out of the cells and from a change in cell sensitivity to vincristine. The amount of ROS arising in cells was determined using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH₂-DA). It was shown that the rate of ROS formation in cells decreases after the addition of serum to the medium and with an increase of the cell number. By the action of hydrogen peroxide, the amount of ROS increases directly with its concentration. Oxidative stress generated by 30–300 μM hydrogen peroxide decreases the MDR of the cells. The effect of hydrogen peroxide increases with the treatment duration and concentration of hydrogen peroxide. MDR determined by the criterion of the efflux of calcein ester from cells is completely suppressed after 1-h exposure to 300 μM hydrogen peroxide. At a concentration of hydrogen peroxide of 60 μM and treatment duration of 1 h, the sensitivity of P388VR cells to vincristine increases to reach the sensitivity of the wild-type P388 cells. Rapid (about 1 h) suppression of MDR is caused by inhibition of the activity of transport proteins. MDR decrease induced by oxidative stress can be used in therapy of tumors resistant to anticancer drugs.     

The effect of oxidative stress on ERalpha and ERbeta expression

The formation of intracellular reactive oxygen and nitrogen species (ROS and RNS) has been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts may cause oxidative damage and be cytotoxic to cells. Recently, it has been established that these oxidants can also act as subcellular messengers in gene regulatory and signal transduction pathways. Estrogen, on the other hand, is known to offer protection from coronary artery diseases in post-menopausal women and to be involved in various ROS-related diseases, such as Alzheimer's and Parkinson's diseases, diabetes and aging. The existence of estrogen receptors in these tissues lead us to investigate whether ROS can regulate their expression. We demonstrated here, for the first time, that oxidative stress induced by hydrogen peroxide (H(2)O(2)), Fe(2+), 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) and activated macrophages, affect the expression of estrogen receptors alpha and beta (ERalpha and ERbeta) differently, demonstrating cell-specific response which can be blocked by antioxidants. This data suggest that oxidative stress and the production of ROS/RNS function as physiological regulators of ERalpha and ERbeta expression. This may provide a new insight into the ERbeta-dependent protective action of estrogen and phytoestrogens in inflammation involving diseases, and may contribute to the development of novel therapeutic treatment strategies.