Programmed cell death during endosperm development

The endosperm of cereals functions as a storage tissue in which the majority of starch and seed storage proteins are synthesized. During its development, cereal endosperm initiates a cell death program that eventually affects the entire tissue with the exception of the outermost cells, which differentiate into the aleurone layer and remain living in the mature seed. To date, the cell death program has been described for maize and wheat endosperm, which exhibits common and unique elements for each species. The progression of endosperm programmed cell death (PCD) in both species is accompanied by an increase in nuclease activity and the internucleosomal degradation of nuclear DNA, hallmarks of apoptosis in animals. Moreover, ethylene and abscisic acid are key to mediating PCD in cereal endosperm. The progression of the cell death program in developing maize endosperm follows a highly organized pattern whereas in wheat endosperm, PCD initiates stochastically. Although the essential characteristics of cereal endosperm PCD are now known, the molecular mechanisms responsible for its execution remain to be identified.     

程序性细胞死亡与肿瘤

程序性细胞死亡（programmed cell death,PCD）是指由基因控制的细胞自主的有序性死亡方式,涉及一系列基因的激活、表达以及调控等。目前,经典细胞凋亡被称为Ⅰ型PCD,而自噬性细胞死亡称为Ⅱ型PCD,坏死样程序性细胞死亡则被称为Ⅲ型PCD,它们在肿瘤的发生、发展及治疗过程中起非常重要的作用。该文结合国内外最新研究进展主要针对不同细胞死亡模式及其相互作用、关键作用蛋白,细胞自噬与肿瘤发生,细胞自噬、凋亡与肿瘤治疗作一简要综述,并展望发展前景,提出在肿瘤治疗中如何利用不同死亡模式的协同作用最大限度地发挥其临床应用价值。     

Programmed cell death of tracheary elements as a paradigm in plants

Plant development involves various programmed cell death (PCD) processes. Among them, cell death occurring during differentiation of procambium into tracheary elements (TEs), which are a major component of vessels or tracheids, has been studied extensively. Recent studies of PCD during TE differentiation mainly using an in vitro differentiation system of Zinnia have revealed that PCD of TEs is a plant-specific one in which the vacuole plays a central role. Furthermore, there are recent findings of several factors that may initiate PCD of TEs and that act at autonomous degradation of cell contents. Herein I summarize the present knowledge about cell death program during TE differentiation as an excellent example of PCD in plants.     

细胞程序性死亡与生态适应

细胞程序性死亡是多细胞有机生命周期中正常的组成部分,细胞程序性死亡过程的存在对生物体是一种保护机制。它是在生物进化过程中形成的,也是生物对环境的适应方式之一。     

Apoptosis: Programmed cell death in health and disease

Apoptosis is a normal physiological cell death process of eliminating unwanted cells from living organisms during embryonic and adult development. Apoptotic cells are characterised by fragmentation of nuclear DNA and formation of apoptotic bodies. Genetic analysis revealed the involvement of many death and survival genes in apoptosis which are regulated by extracellular factors. There are multiple inducers and inhibitors of apoptosis which interact with target cell specific surface receptors and transduce the signal by second messengers to programme cell death. The regulation of apoptosis is elusive, but defective regulation leads to aetiology of various ailments. Understanding the molecular mechanism of apoptosis including death genes, death signals, surface receptors and signal pathways will provide new insights in developing strategies to regulate the cell survival/death. The current knowledge on the molecular events of apoptotic cell death and their significance in health and disease is reviewed.     

Cell death of barley aleurone protoplasts is mediated by reactive oxygen species

The barley aleurone layer is a terminally differentiated secretory tissue whose activity is hormonally controlled. The plant hormone gibberellic acid (GA) stimulates the secretion of hydrolytic enzymes and triggers the onset of programmed cell death (PCD). Abscisic acid (ABA) antagonizes the effects of GA and inhibits enzyme secretion and PCD. Reactive oxygen species (ROS) are key players in many types of PCD, and data presented here implicate ROS in hormonally regulated death of barley aleurone cells. Incubation of aleurone layers or protoplasts in H(2)O(2)-containing media results in death of GA-treated but not ABA-treated aleurone cells. Cells that are programmed to die are therefore less able to withstand ROS than cells that are programmed to remain alive. Illumination of barley aleurone protoplasts with blue or UV-A light results in a rapid increase in intracellular H(2)O(2) production. GA-treated protoplasts die rapidly in response to this increase in intracellular H(2)O(2) production, but ABA-treated protoplasts do not die. The rate of light-induced death could be slowed by antioxidants, and incubating protoplasts in the dark with the antioxidant butylated hydroxy toluene reduces the rate of hormonally induced death. Taken together, these data demonstrate that GA-treated aleurone protoplasts are less able than ABA-treated protoplasts to tolerate internally generated or exogenously applied H(2)O(2), and strongly suggest that ROS are components of the hormonally regulated cell death pathway in barley aleurone cells.     

Programmed cell death in cell cultures

In plants most instances of programmed cell death (PCD) occur in a number of related, or neighbouring, cells in specific tissues. However, recent research with plant cell cultures has demonstrated that PCD can be induced in single cells. The uniformity, accessibility and reduced complexity of cell cultures make them ideal research tools to investigate the regulation of PCD in plants. PCD has now been induced in cell cultures from a wide range of species including many of the so-called model species. We will discuss the establishment of cell cultures, the fractionation of single cells and isolation of protoplasts, and consider the characteristic features of PCD in cultured cells. We will review the wide range of methods to induce cell death in cell cultures ranging from abiotic stress, absence of survival signals, manipulation of signal pathway intermediates, through the induction of defence-related PCD and developmentally induced cell death.     

Programmed cell death in neurotumour cells involves the generation of ceramide

Ceramide has been typically thought of as the membrane anchor for the carbohydrate in glycosphingolipids but many studies have suggested that it may cause apoptosis. Apoptosis or programmed cell death (PCD) is thought to be responsible for the death of one-half of neurons surviving the development of the nervous system. The potential involvement of the sphingomyelin-ceramide signaling process as an integral part of PCD was therefore examined in several neurotumour cell lines. We show that synthetic C2-ceramide (N-acetylsphingosine), a soluble ceramide analogue, can rapidly trigger PCD in these cells, characterized by: 1) classic DNA laddering on agarose gels; 2) DNA fragmentation as determined by Hoechst Dye; and 3) cell viability (mitochondrial function and intact nuclei) assays. We report that staurosporine can both activate PCD (by all three criteria above) in neurotumour cells and increase both the formation of ceramide and ceramide mass. Both ceramide formation and the induction of PCD were further enhanced by the co-addition of a ceramidase inhibitor oleoylethanolamine (25 µM). Staurosporine and oleoylethanolamine were similarly effective in inducing ceramide formation and PCD in immortalized hippocampal neurons (HN-2) and immortalized dorsal root ganglion cells (F-11). Our data suggests that formation of ceramide is a key event in the induction of PCD in neuronally derived neurotumour cells.Abbreviations PCD programmed cell death - PKC protein kinase C - HPTLC high-performance thin-layer chromatography - DETAPAC diethylenetriaminepentaacetic acid - DMEM Dubelco's modified Eagle's medium - FCS fetal calf serum - PBS phosphate-buffered saline - DAG diacylglycerol - DDI distilled-deionized - Cer ceramide - SM sphingomyelin Dedicated to Dr Sen-itiroh Hakomori in celebration of his 65th birthday.     

泛素/26S蛋白酶体系统介导的细胞程序化死亡

在一定的生理或者病理条件下,细胞为了自身发育或者抵御不良刺激,会采取细胞程序化死亡（programmed cell death,PCD）的方式结束生命。泛素/26S蛋白酶体系统（ubiquitin-26S proteasome system,UPS）作为生物体中重要的翻译后蛋白质调节系统,对PCD起着关键的调节作用。该文介绍UPS通过两条细胞凋亡信号转导通路以及天冬氨酸特异性半胱氨酸蛋白酶来调控PCD的研究进展。     

Programmed cell death in plants: distinguishing between different modes

Programmed cell death (PCD) in plants is a crucial componentof development and defence mechanisms. In animals, differenttypes of cell death (apoptosis, autophagy, and necrosis) havebeen distinguished morphologically and discussed in these morphologicalterms. PCD is largely used to describe the processes of apoptosisand autophagy (although some use PCD and apoptosis interchangeably)while necrosis is generally described as a chaotic and uncontrolledmode of death. In plants, the term PCD is widely used to describemost instances of death observed. At present, there is a vastarray of plant cell culture models and developmental systemsbeing studied by different research groups and it is clear fromwhat is described in this mass of literature that, as with animals,there does not appear to be just one type of PCD in plants.It is fundamentally important to be able to distinguish betweendifferent types of cell death for several reasons. For example,it is clear that, in cell culture systems, the window of timein which ‘PCD’ is studied by different groups varieshugely and this can have profound effects on the interpretationof data and complicates attempts to compare different researcher'sdata. In addition, different types of PCD will probably havedifferent regulators and modes of death. For this reason, inplant cell cultures an apoptotic-like PCD (AL-PCD) has beenidentified that is fairly rapid and results in a distinct corpsemorphology which is visible 4–6 h after release of cytochromec and other apoptogenic proteins. This type of morphology, distinctfrom autophagy and from necrosis, has also been observed inexamples of plant development. In this review, our model systemand how it is used to distinguish specifically between AL-PCDand necrosis will be discussed. The different types of PCD observedin plants will also be discussed and the importance of distinguishingbetween different forms of cell death will be highlighted. Key words: Apoptosis, apoptosis-like programmed cell death (AL-PCD), Arabidopsis, autophagy, mitochondria, necrosis, programmed cell death (PCD) Received 5 June 2007; Revised 13 September 2007 Accepted 20 September 2007     

Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a pathological condition recognized by menstrual cycle irregularities, androgen excess, and polycystic ovarian morphology, affecting a significant proportion of women of childbearing age and accounting for the most prevalent cause of anovulatory sterility. In addition, PCOS is frequently accompanied by metabolic and endocrine disturbances such as obesity, dyslipidemia, insulin resistance, and hyperinsulinemia, indicating the multiplicity of mechanisms implicated in the progression of PCOS. However, the exact pathogenesis of PCOS is yet to be elucidated. Programmed cell death 4 (PDCD4) is a ubiquitously expressed protein that contributes to the regulation of various cellular processes, including gene expression, cell cycle progression, proliferation, and apoptosis. Despite some disparities concerning its exact cellular effects, PDCD4 is generally characterized as a protein that inhibits cell cycle progression and proliferation and instead drives the cell into apoptosis. The apoptosis of granulosa cells (GCs) is speculated to take a major part in the occurrence and progression of PCOS by ceasing antral follicle development and compromising oocyte competence. Given the possible involvement of GC apoptosis in the progression of PCOS, as well as the contribution of PDCD4 to the regulation of cell apoptosis and the development of metabolic diseases, the current review aimed to discuss whether or how PDCD4 can play a role in the pathogenesis of PCOS by affecting GC apoptosis.     

Programmed cell death and tissue remodelling in plants

The use of programmed cell death (PCD) to remodel plants at the cellular, tissue, and organ levels is particularly fascinating and occurs in such processes as tracheary element differentiation, lysigenous aerenchyma formation, development of functionally unisexual flowers from bisexual floral primordia, and leaf morphogenesis. The formation of complex leaf shape through the use of PCD is a rare event across vascular plants and occurs only in a few species of Monstera and related genera, and in the lace plant (Aponogeton madagascariensis). During early development, the lace plant leaf forms a pattern of equidistantly positioned perforations across the surface of the leaf, giving it a lattice-like appearance. Due to the accessibility and predictability of this process, the lace plant provides highly suitable material for the study of developmentally regulated PCD in plants. A sterile lace plant culture system has been successfully established, providing material free of micro-organisms for experimental study. The potential role of ethylene and caspase-like activity in developmentally regulated PCD in the lace plant is currently under investigation, with preliminary results indicating that both may play a role in the cell death pathway.     

Regulation of programmed cell death in maize endosperm by abscisic acid

Cereal endosperm undergoes programmed cell death (PCD) during its development, a process that is controlled, in part, by ethylene. Whether other hormones influence endosperm PCD has not been investigated. Abscisic acid (ABA) plays an essential role during late seed development that enables an embryo to survive desiccation. To examine whether ABA is also involved in regulating the onset of PCD during endosperm development, we have used genetic and biochemical means to disrupt ABA biosynthesis or perception during maize kernel development. The onset and progression of cell death, as determined by viability staining and the appearance of internucleosomal DNA fragmentation, was accelerated in developing endosperm of ABA-insensitive vp1 and ABA-deficient vp9 mutants. Ethylene was synthesized in vp1 and vp9 mutant kernels at levels that were 2–4-fold higher than in wild-type kernels. Moreover, the increase and timing of ethylene production correlated with the premature onset and accelerated progression of internucleosomal fragmentation in these mutants. Treatment of developing wild-type endosperm with fluridone, an inhibitor of ABA biosynthesis, recapitulated the increase in ethylene production and accelerated execution of the PCD program that was observed in the ABA mutant kernels. These data suggest that a balance between ABA and ethylene establishes the appropriate onset and progression of programmed cell death during maize endosperm development.     

Programmed cell death in Bradysia hygida (Diptera, Sciaridae) salivary glands presents apoptotic features

In this work, we present biochemical and morphological evidence that the final steps of programmed cell death (PCD) in the salivary glands of the inferior Diptera, Bradysia hygida, present apoptotic characteristics. In B. hygida, elimination of salivary glands is preceded by the establishment of a typical pattern of protein synthesis; increase in caspase activity; decrease in cell volume; nuclear pyknosis; nuclear DNA breakage; changes in the actin cytoskeleton; and most importantly, destruction of giant cells via formation of apoptotic bodies containing broken DNA or cytoplasm remains. Thus, elimination of B. hygida salivary glands by this process suggests that such mode of PCD is also involved in the destruction of entire organs in insects and, therefore, adds more complexity to the regulation of tissue elimination during development.     

Programmed cell death in spinal cord injury pathogenesis and therapy

Spinal cord injury (SCI) always leads to functional deterioration due to a series of processes including cell death. In recent years, programmed cell death (PCD) is considered to be a critical process after SCI, and various forms of PCD were discovered in recent years, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis. Unlike necrosis, PCD is known as an active cell death mediated by a cascade of gene expression events, and it is crucial for elimination unnecessary and damaged cells, as well as a defence mechanism. Therefore, it would be meaningful to characterize the roles of PCD to not only enhance our understanding of the pathophysiological processes, but also improve functional recovery after SCI. This review will summarize and explore the most recent advances on how apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis are involved in SCI. This review can help us to understand the various functions of PCD in the pathological processes of SCI, and contribute to our novel understanding of SCI of unknown aetiology in the near future.     

Programmed cell death during embryogenesis in maize

Programmed cell death (PCD) in plants is considered an integral part of development. Evidence of DNA fragmentation, occurring at specific sites and times during embryo formation in maize (Zea mays L.), was obtained using terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end labelling (TUNEL) and by genomic DNA ladder detection. During the crucial period of elaboration of the primary shoot and root axis (14-20 d after pollination), TUNEL-positive nuclei are present in the scutellum, coleoptile, root cap and principally in the suspensor. Additional evidence of a form of programmed cell death occurring in these tissues comes from the detection of a DNA ladder. Upon completion of the differentiation process, all embryonic cells are TUNEL-negative, indicating that possible programmed cell death events during maize embryogenesis are confined to structures or organs that do not contribute to the adult plant body.     

Interdigital cell death function and regulation: new insights on an old programmed cell death model

Interdigital cell death (ICD) is the oldest and best-studied model of programmed cell death (PCD) in vertebrates. The classical view of ICD function is the separation of digits by promotion of tissue regression. However, in addition, ICD can contribute to digit individualization by restricting interdigital tissue growth. Depending on the species, the relative contribution of either regression or growth-restricting functions of ICD to limb morphogenesis may differ. Under normal conditions, most cells appear to die by apoptosis during ICD. Accordingly, components of the apoptotic machinery are found in the interdigits, though their role in the initiation and execution of cell death is yet to be defined. Fgf8 has been identified as a survival factor for the distal mesenchymal cells of the limb such that ICD can initiate following specific downregulation of Fgf8 expression in the ectoderm overlying the interdigital tissue. On the other hand, Bmps may promote cell death directly by acting on the interdigital tissue, or indirectly by downregulating Fgf8 expression in the ectoderm. In addition, retinoic acid can activate ICD directly or through a Bmp-mediated mechanism. Interactions at different levels between these factors establish the spatiotemporal patterning of ICD activation. Defining the regulatory network behind ICD activation will greatly advance our understanding of the mechanisms controlling PCD in general.