信号分子介导藻类细胞程序性死亡的研究进展

藻类是水生态系统中的重要初级生产者, 在物质转换和能量迁移过程中发挥重要作用。细胞程序性死亡(PCD)作为一种细胞自我调控的死亡模式, 受到多种信号分子的控制。研究发现藻类细胞在遭受环境胁迫的情况下, 在形态和生理上均表现出类PCD的特征, 同时伴随着活性氧/一氧化氮/钙离子(ROS/NO/Ca2+)水平的变化。研究认为, ROS/NO/Ca2+作为信号分子介导藻细胞内的caspase-like酶活性变化, 从而触发藻细胞的类程序性死亡。然而, 对信号分子是如何在环境胁迫下的藻类细胞中引发类PCD仍知之甚少。文章综述了信号分子ROS/NO/Ca2+介导藻类类PCD的研究进展以及信号分子间的级联关系, 并对今后类PCD在该领域待开展的研究进行了展望。     

液泡信号通路依赖的细胞程序性死亡研究进展

液泡是植物细胞专一性器官之一,具有多种功能,参与细胞内环境调节和细胞解毒等过程。研究表明,液泡在植物细胞程序性死亡（programmed cell death,PCD）中具有重要作用。在液泡介导的PCD过程中,液泡加工酶（vacuolar processing enzyme,VPE）的调控和激活是PCD的关键环节。着眼于液泡信号通路依赖的PCD,对相关细胞事件和分子调控机制进行了讨论,并对未来的研究方向作了展望,以期能推进PCD机制解明。     

植物细胞程序性死亡研究进展

植物细胞死亡分为坏死和程序性死亡。细胞程序性死亡是具有信号或一系列分子参与,并且由细胞内在的死亡程序介导的有序过程。它在植物生长发育和抵御外界胁迫中具有重要作用。简要介绍了植物PCD的特征,对植物PCD中的信号分子和类caspase的作用等进行了综述,并对植物PCD存在的问题进行分析和展望,为深入研究植物PCD提供参考。     

胸腺细胞的选择与程序性细胞死亡

胸腺通过阳性和阴性选择作用,保留有功能的并对自身耐受的T细胞,同时通过启动程序性细胞死亡（programmedcelldeath,PCD）机制消除无功能的或对自身有反应性的T细胞。参与胸腺细胞PCD调节的因素中包括胸腺基质细胞和膜分子的作用。胸腺内细胞发生PCD的机理十分复杂。本文从两种选择中PCD出现的特点,PCD与选择作用之间的关系,以及在T细胞耐受形成中PCD的作用等方面,在细胞和分子水平上描述当前这一领域中的研究进展,并提出了若干仍需解决的关键问题。     

HIF-NOS信号通路对哺乳动物卵巢NO依赖性功能的调控作用

一氧化氮(NO)作为气体明星分子和信号分子,在哺乳动物体内不同的生理调节过程中具有非常重要的作用,尤其是哺乳动物卵巢功能的调控.一氧化氮合酶(NOS)是NO合成的限速酶,是调节NO合成的关键环节,也是NO依赖性功能调控的重要环节.因此,调节NOS转录/合成的信号通路对哺乳动物卵巢NO依赖性功能具有至关重要的调控作用.最近的研究发现,缺氧诱导因子(HIF)作为转录因子,参与许多与缺氧相关靶基因的转录调控,如NOS和血管内皮生长因子(VEGF)等.本文一方面描述了NO合成及其调控的分子机制,另一方面阐明了HIF作为转录因子对NOS的转录调控,从而揭示HIF在NO依赖性卵巢功能调控中的重要作用,同时为进一步研究哺乳动物卵巢功能的调控提供新的研究方向和理论基础.     

NO在植物中的调控作用

一氧化氮（NO）是一种易扩散的生物活性分子,是生物体内重要的信号分子。植物细胞通过NO合酶、硝酸还原酶、或非生化反应途径产生NO。NO参与植物生长发育调控和对生物与非生物环境胁迫的应答反应,大量证据表明NO是植物防御反应中的关键信使,其信号转导机制也受到越来越多的关注。本文主要通过讨论NO的产生、对植物生长周期的影响、在植物代谢中的信号调节以及参与细胞凋亡来阐述NO在植物中的作用。     

气体信号分子NO、CO和H_2S的生物学研究进展

一氧化氮(nitric oxide,NO)、一氧化碳(carbon monoxide,CO)和硫化氢(hydrogen sulfide,H2S)这三种大气组分相继被发现具有重要的生物活性,参与多种病理生理过程。近年来,关于NO、CO的研究日趋成熟,而H2S作为新发现的气体信号分子在各个系统中的作用也日益受到重视。这三种信号分子的生物学特性具有很多异同点,且相互调控。本文将在合成代谢、生物学功能、分子靶标和信号机制等方面系统地介绍这三种分子在生命和医学领域的研究进展。     

一氧化氮与神经血管单元的关联性及相关药物研究进展

一氧化氮（NO）作为一种重要的信号分子,对中枢神经系统具有重要影响。神经血管单元是近年来提出的从整体上描述中枢神经 系统的新概念,NO对中枢系统的作用是多层次多角度的,NO与神经血管单元这个整体及其各组成单元均密切相关。综述NO及其合成酶 的功能,在中枢神经系统疾病中NO与神经血管单元的相互作用关系及以NO信号通路为靶点的相关药物研究进展。     

植物细胞程序性死亡——一个新兴的研究领域

近年来,越来越多的证据表明,植物细胞在生理、病理或逆境条件下可发生程序性死亡(Programmed Cell Death．PCD)。本文详细描述了植物PCD的形态和生化特征、生理功能及其研究意义,并把这些方面与动物PCD做了比较。另外,虽然植物PCD的研究尚处于起步阶段,本文还是对其可能的信号传导机制、遗传调控以及PCD的起源与进化作了探讨,并提出了植物PCD的研究战略。具体说来有以下几个方面：1形态和生化特征：目前,植物PCD的研究主要还集中于形态和生化方面的描述。各种条件下的植物PCD在形态和生化特征上都或多或少地与动物细胞凋亡存在差异,并不符合动物细胞凋亡定义的全部内容。并且不同植物PCD类型相互之间也存在着较大的不同。尽管如此,动植物PCD在形态和生化方面还是存在许多相似之处。无炎症反应、DNA的特异片段化以及核酸内切酶和蛋白酶活性的升高在植物中也依然是区别PCD与细胞坏死(necrosis)的形态和生化依据。2．分子水平上,植物PCD也涉及到许多信号分子和特定基因参与调控的信号传导途径。但到目前为止,已分离的与植物PCD直接相关的基因只有ACD2、Dad1等少数几个．尽管己证明一些信号分子如活性氧种类(reactive oxygen species,ROSs)、Ca2 、植物激素等参与了植物PCD的信号传导,而对其信号传导途径及机制还一无所知。不过,这些信号分子及几个相关基因的分离将有助于阐明植物PCD的信号传导机制。并且,从已有的证据看来,参与PCD的基因以及一些信号分子在动植物中具有相当的保守性,因此推测动植物PCD可能存在共同的基因调控规律及信号传导机制。近来,在HR以及发育过程中的PCD中检测到有类似caspase的蛋白酶的参与。这些证据表明,PCD在分子水平上具有一定的保守性,为PCD的起源与进化提供了有力的证据。3．植物PCD的生理功能也与动物的相似。在植物的生殖、发育,生长、衰老以及植物抗病、抗逆等整个生命过程中,PCD担负着与细胞增殖同等重要的生理功能。因此,无论从理论还是从实践上,植物PCD都具有重要的研究意义。4．纵观各方面的证据可以推测,PCD起源于原核生物,并随着生物的进化而进化。在生物进化树的分支上,已发现不同类型的PCD形式。结论：许多内因或外因都能打破植物的体内平衡,最终导致细胞分化、增殖、静止或死亡。纵观各种生,病理及逆境胁迫下的植物PCD可以看出,虽然它们之间有着较大的不同,并且都与动物细胞凋亡存在较大的差异、那些共同的形态和生化特征应该便可以做为PCD的定义内容。     

一氧化氮在植物抗病反应中的信号作用

近年来的研究发现,一氧化氮（nitic oxide,NO)在植物抗病反应中具有重要作用,本文概述了植物中NO的来源,NO在植物抗病反应中的信号传导作用,NO与植物中其它信号分子之间的相互作用以及NO的研究进展。     

Nitric oxide: promoter or suppressor of programmed cell death?

Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and-independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.     

Sorting out the role of nitric oxide in cadmium-induced Arabidopsis thaliana programmed cell death

As a vital cell-signaling molecule, nitric oxide (NO) has been reported to regulate toxic metal responses in plants. Our recent report has suggested that caspase-3-like protease activation was detected in Arabidopsis (Arabidopsis thaliana) after Cd²⁺ treatment. NO contributed caspase-3-like protease activation in Cd²⁺ induced Arabidopsis thaliana programmed cell death (PCD), which was mediated by MPK6. It was first shown that NO promotes Cd²⁺-induced Arabidopsis PCD by promoting MPK6-mediated caspase-3-like activation. Our study contributed to the understanding of NO signaling pathway in Cd²⁺-induced Arabidopsis thaliana PCD. Although several studies have revealed that NO regulates plant PCD, compared with the study of signaling pathways involved in animal cell apoptosis, the mechanism of NO function still remains elusive and the molecular mechanisms of MAPK are far from clear in Cd²⁺-induced PCD. By using the fluorescence techniques and the Arabidopsis seedlings as the reference model, the subsequent researches have been performed to obtain comprehensive understanding of Cd²⁺-induced plant PCD.     

Nitric oxide is involved in establishing the balance between cell cycle progression and cell death in the developing neural tube

Endogenous nitric oxide (NO) has recently been shown to affect cell cycle progression in the neural tube (NT) of the chick embryo. High NO levels trigger entry into S phase basally, while low NO levels facilitate mitosis apically. Here, we further explore the involvement of NO in determining cell numbers in the chick NT. In addition to the effect of short-term (6 h) NOS inhibition, we have observed a concomitant decrease in programmed cell death (PCD). Paradoxically, long-term (12 h) NOS inhibition caused an increase in PCD to compensate for the high proliferation rate under these conditions. Long-term treatment with a NO donor caused a decrease in S phase and increased PCD. The effects produced by the NO donor could be alleviated by folic acid that facilitated entry into S phase and prevented PCD. The effects produced by NOS inhibition (12 h) could be overcome by an embryo extract, used as a source of extracellular survival factors that enhanced proliferation and prevented PCD. Taken together, these data demonstrate that changing endogenous NO levels affect the balance between cell proliferation and PCD in NT of the developing chick embryo.     

铝诱导植物程序性细胞死亡信号转导的研究进展

铝是制约酸性土壤上作物生产的主要因素。铝诱导氧化胁迫产生大量活性氧/一氧化氮,引起胞质钙超载,通过线粒体信号转导途径激发相关凋亡基因,从而引起细胞主动死亡,以减轻铝对植物的进一步毒害。本文综述了铝诱导程序性细胞死亡的信号分子、相关基因以及信号转导途径,对未来的研究方向提出了展望,为深入研究植物铝毒害机理和耐铝机制提供参考。     

Critical Temporal Modulation of Neuronal Programmed Cell Injury

1. As a free radical, nitric oxide (NO) may be toxic to neurons through mechanisms that directly involve DNA damage. Lubeluzole, a novel benzothiazole compound, has recently been demonstrated to be neuroprotective through the signal transduction pathways of NO. We therefore examined whether neuroprotection by lubeluzole was dependent upon the molecular pathways of programmed cell death (PCD).2. In primary hippocampal neurons, evidence of PCD was determined by hematoxylin and eosin (H&E) stain, transmission electron microscopy, and annexin-V binding. NO administration with the NO generators sodium nitroprusside (300 M) or SIN-1 (300 M) directly induced PCD.3. Neurons positive for PCD increased from 22 ± 3% (untreated) to 72 ± 3% (NO) over a 24-hr period. Coadministration of NO and lubeluzole (750 nM), a neuroprotective concentration, actively decreased PCD expression on H&E stain from 72 ± 3% (NO only) to 25 ± 3% (NO and lubeluzole). Significant reduction in DNA fragmentation by lubeluzole also was evident on electron microscopy. Application of lubeluzole in concentrations that were not neuroprotective or administration of the biologically inactive R-isomer did not significantly alter NO-induced PCD, suggesting that neuroprotection by lubeluzole was intimately linked to the modulation of PCD. Lubeluzole also was able to prevent the initial stages of cellular membrane inversion labeled with annexin-V binding, an early and sensitive indicator of PCD. Interestingly, the critical period for lubeluzole to reverse PCD induction appeared to be within the first 4 hr following NO exposure.4. Further investigation into the neuroprotective pathways that alter PCD may provide greater insight into the molecular mechanisms that ultimately determine neuronal injury.     

Changes in the antioxidant systems as part of the signaling pathway responsible for the programmed cell death activated by nitric oxide and reactive oxygen species in tobacco Bright-Yellow 2 cells

Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed.     

植物在逆境胁迫中的细胞程序性死亡

细胞程序性死亡(programmed cell death,PCD)是一种由基因控制的、主动的细胞死亡过程,它对植物正常生长发育起重要作用.在逆境胁迫因子如病原体、高盐、低氧、低温、热激和金属离子等作用下,植物为了抵御不良环境的侵害,以活性氧、Ca2+、乙烯和NO等为信号因子,诱导植物体的特定部位发生PCD,形成细胞主动死亡,从而避免逆境对其他组织进一步伤害,并使植物获得对不良环境的适应性.对植物PCD的一般特征、环境胁迫因子及诱导PCD信号分子等进行了综述,为在逆境条件下深入研究植物细胞程序性死亡提供参考.     

NO way to live; the various roles of nitric oxide in plant-pathogen interactions

Nitric oxide has attracted considerable interest from plant pathologists due its established role in regulating mammalian anti-microbial defences, particularly via programmed cell death (PCD). Although NO plays a major role in plant PCD elicited in response to certain types of pathogenic challenge, the race-specific hypersensitive response (HR), it is now evident that NO also acts in the regulation of non-specific, papilla-based resistance to penetration by plant cells that survive attack and, possibly, in systemic acquired resistance. Equally, the potential roles of NO signalling/scavenging within the pathogen are being recognized. This review will consider key defensive roles played by NO in living cells during plant-pathogen interactions, as well as in those undergoing PCD.     

Nitric oxide acts as an antioxidant and delays programmed cell death in barley aleurone layers

Nitric oxide (NO) is a freely diffusible, gaseous free radical and an important signaling molecule in animals. In plants, NO influences aspects of growth and development, and can affect plant responses to stress. In some cases, the effects of NO are the result of its interaction with reactive oxygen species (ROS). These interactions can be cytotoxic or protective. Because gibberellin (GA)-induced programmed cell death (PCD) in barley (Hordeum vulgare cv Himalaya) aleurone layers is mediated by ROS, we examined the effects of NO donors on PCD and ROS-metabolizing enzymes in this system. NO donors delay PCD in layers treated with GA, but do not inhibit metabolism in general, or the GA-induced synthesis and secretion of alpha-amylase. alpha-Amylase secretion is stimulated slightly by NO donors. The effects of NO donors are specific for NO, because they can be blocked completely by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. The antioxidant butylated hydroxy toluene also slowed PCD, and these data support our hypothesis that NO is a protective antioxidant in aleurone cells. The amounts of CAT and SOD, two enzymes that metabolize ROS, are greatly reduced in aleurone layers treated with GA. Treatment with GA in the presence of NO donors delays the loss of CAT and SOD. We speculate that NO may be an endogenous modulator of PCD in barley aleurone cells.