Regulation and execution of programmed cell death in response to pathogens, stress and developmental cues

Recent studies have expanded our view of the interactions between small molecule signals that regulate the hypersensitive response and other forms of cell suicide in plants. The mitochondrion has received increasing support as a mediator of at least some forms of programmed cell death in plants. In addition, new information provides a glimpse of how plant hormone signaling may be integrated with extensive autolysis, sensitivity to reactive oxygen intermediates and cell death.     

Dinitro-o-cresol induces apoptosis-like cell death but not alternative oxidase expression in soybean cells

In plants, programmed cell death is thought to be activated during differentiation and in response to biotic and abiotic stresses. Although its mechanisms are far less clear, several morphological and biochemical features have been described in different experimental systems, including DNA laddering and cytosolic protease activation. Moreover, plant mitochondria have an alternative terminal oxidase (AOX), which is thought to be involved in protection against increased reactive oxygen species production, perhaps representing a mechanism to prevent programmed cell death. In this study, we analysed cell death induced by the herbicide dinitro-o-cresol (DNOC) in soybean (Glycine max) suspension cell cultures and evaluated biochemical and molecular events associated with programmed cell death. AOX capacity and expression were also determined. DNOC-treated cells showed fragmented nuclear DNA as assessed by an in situ assay that detects 3'-OH ends. In addition, specific colorimetric assays and immunoblot analysis revealed activation of caspase-3-like proteins and release of cytochrome c from mitochondria, respectively, confirming the apoptotic-like phenotype. Surprisingly, AOX capacity and protein levels decreased in DNOC-treated cells, suggesting no association between cell death and AOX under these experimental conditions. In conclusion, the results show that DNOC induces programmed cell death in soybean cells, suggesting that plants and animals might share similar pathways. Further, the role of AOX in cell death has not been confirmed, and may depend on the nature and intensity of stress conditions.     

被子植物有性生殖过程中的细胞程序死亡

细胞程序死亡是植物发育过程中的一种普遍现象。早就认识到高等植物生殖器官中一些细胞的死亡对植物有性生殖具有重要作用。这些细胞的死亡过程与动物组织中的细胞程序死亡基本相同。但植物体内诱导生殖细胞程序死亡的信号及其传导系统则显示出其特点 ,有些还表现出雌、雄性细胞的相互作用。探索植物生殖过程中的细胞程序死亡现象将有利于澄清植物生殖过程中的一些机理问题 ,使过去的细胞学研究结果深入到分子水平进行探讨     

On the origin, evolution, and nature of programmed cell death: a timeline of four billion years

Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new level of complexity, with important therapeutic implications, has begun to emerge, suggesting (i) that several different self-destruction pathways may exist and operate in parallel in our cells, and (ii) that molecular effectors of cell suicide may also perform other functions unrelated to cell death induction and crucial to cell survival. In this review, I will argue that this new level of complexity, implying that there may be no such thing as a 'bona fide' genetic death program in our cells, might be better understood when considered in an evolutionary context. And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms.     

Markers for hypersensitive response and senescence show distinct patterns of expression

Controlled cellular suicide is an important process that can be observed in various organs during plant development. From the generation of proper sexual organs in monoecious plants to the hypersensitive response (HR) that occurs during incompatible pathogen interactions, programmed cell death (PCD) can be readily observed. Although several biochemical and morphological parameters have been described for various types of cell death in plants, the relationships existing between those different types of PCD events remain unclear. In this work, we set out to examine if two early molecular markers of HR cell death (HIN1 and HSR203J) as well as a senescence marker (SAG12) are coordinately induced during these processes. Our result indicates that although there is evidence of some cross-talk between both cell death pathways, spatial and temporal characteristics of activation for these markers during hypersensitive response and senescence are distinct. These observations indicate that these markers are relatively specific for different cell death programs. Interestingly, they also revealed that a senescence-like process seems to be triggered at the periphery of the HR necrotic lesion. This suggests that cells committed to die during the HR might release a signal able to induce senescence in the neighboring cells. This phenomenon could correspond to the establishment of a second barrier against pathogens. Lastly, we used those cell death markers to better characterize cell death induced by copper and we showed that this abiotic induced cell death presents similarities with HR cell death.     

Selective "death programs" or pleiotropic"life programs"? Looking for programmed cell death in the light of evolution

"Nothing in biology makes sense except in the light of evolution", wrote Theodosius Dobzhansky, one of the founders of the Modern Synthesis that led to the unification of evolutionary theory and genetics in the midst of the 20th century. Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new, and somehow puzzling level of complexity has recently begun to emerge, suggesting i) that several different self destruction pathways may exist and operate in parallel in our cells, and ii) that molecular effectors of cell suicide might also perform other functions unrelated to cell death induction and crucial to cell survival, such as cell differentiation, metabolism, and the regulation of the cell cycle. These new findings, with important physiopathological and therapeutic implications, seem at odds with the paradigm of programmed cell death derived from the studies of Caenorhabditis elegans, which led to the concept of the existence of selective, bona fide death genes that emerged and became selected for their sole capacity to execute or repress cell death. In this review, I will argue that this new level of complexity might only make sense and be understood when considered in a broader evolutionary context than that of our phylogenetic divergence from C. elegans. A new view of the regulated cell death pathways emerges when one attempts to ask the question of when and how they may have become selected during a timeline of 4 billion years, at the level of ancestral single-celled organisms, including the bacteria. I will argue that there may be no such thing as a bona fide genetic cell death program. Rather, in the framework of a model that I have termed the "original sin" hypothesis, I have proposed the existence of an initial pleiotropy of the molecular tools involved in the control and execution of self-destruction--an ancestral involvement in both pro-life and pro-death activities. I will discuss how this hypothesis may be reconciled with the C. elegans paradigm of programmed cell death. Finally I will discuss how an ancestral level of pleiotropic functions of the molecular tools involved in the control of cell death, aging and genetic diversification might have favored their initial selection, their constant availability for de novo selection, and their progressive propagation in most--if not all--species during the course of evolution.     

Oxidant and antioxidant signalling in plants: a re-evaluation of the concept of oxidative stress in a physiological context

While the chemical nature of reactive oxygen species (ROS) dictates that they are potentially harmful to cells, recent genetic evidence suggests that in planta purely physicochemical damage may be much more limited than previously thought. The most potentially deleterious effect of ROS under most conditions is that at high concentrations they trigger genetically programmed cell suicide events. Moreover, because plants use ROS as second messengers in signal transduction cascades in processes as diverse as mitosis, tropisms and cell death, their accumulation is crucial to plant development as well as defence. Direct ROS signal transduction will ensue only if ROS escape destruction by antioxidants or are otherwise consumed in a ROS cascade. Thus, the major low molecular weight antioxidants determine the specificity of the signal. They are also themselves signal-transducing molecules that can either signal independently or further transmit ROS signals. The moment has come to re-evaluate the concept of oxidative stress. In contrast to this pejorative or negative term, implying a state to be avoided, we propose that the syndrome would be more usefully described as 'oxidative signalling', that is, an important and critical function associated with the mechanisms by which plant cells sense the environment and make appropriate adjustments to gene expression, metabolism and physiology.     

The autophagosomal-lysosomal compartment in programmed cell death

In the last decade a tremendous progress has been achieved in understanding the control of apoptosis by survival and death factors as well as the molecular mechanisms of preparation and execution of the cell's suicide. However, accumulating evidence suggests that programmed cell death (PCD) is not confined to apoptosis but that cells use different pathways for active self-destruction as reflected by different morphology: condensation prominent, type I or apoptosis; autophagy prominent, type II; etc. Autophagic PCD appears to be a phylogenetically old phenomenon, it may occur in physiological and disease states. Recently, distinct biochemical and molecular features have been be assigned to this type of PCD. However, autophagic and apoptotic PCD should not be considered as mutually exclusive phenomena. Rather, they appear to reflect a high degree of flexibility in a cell's response to changes of environmental conditions, both physiological or pathological. Furthermore, recent data suggest that diverse or relatively unspecific signals such as photodamage or lysosomotropic agents may be mediated by lysosomal cysteine proteases (cathepsins) to caspases and thus, apoptosis. The present paper reviews morphological, functional and biochemical/molecular data suggesting the participation of the autophagosomal-lysosomal compartment in programmed cell death.     

Programmed cell death during plant growth and development

This review describes programmed cell death as it signifies the terminal differentiation of cells in anthers, xylem, the suspensor and senescing leaves and petals. Also described are cell suicide programs initiated by stress (e.g., hypoxia-induced aerenchyma formation) and those that depend on communication between neighboring cells, as observed for incompatible pollen tubes, the suspensor and synergids in some species. Although certain elements of apoptosis are detectable during some plant programmed cell death processes, the participation of autolytic and perhaps autophagic mechanisms of cell killing during aerenchyma formation, tracheary element differentiation, suspensor degeneration and senescence support the conclusion that nonapoptotic programmed cell death pathways are essential to normal plant growth and development. Heterophagic elimination of dead cells, a prominent feature of animal apoptosis, is not evident in plants. Rather autolysis and autophagy appear to govern the elimination of cells during plant cell suicide.     

Pathogen-induced programmed cell death in plants,a possible defense mechanism

As much as the definition of life may be controversial, the definition of death also may prove problematic. In recent years it became apparent that the death of a living cell may follow more than one possible scenario: it may result from an externally applied physical injury (an accidental death), or it may be the outcome of activating an internal pathway for cell suicide (a programmed death). That cells can participate in their own execution may indicate that certain types of cell deaths that were previously considered to be caused by foreign agents such as pathogens or drugs may actually result from the activation of a programmed cell death pathway that is normally latent in cells. Here, we describe the activation of such a cell suicide pathway in plant cells upon the recognition of an invading pathogen. We discuss the possible use of this pathway as a defense mechanism against infection and the possibility that in many ways the use of this type of cell death in plants is functionally analogous to that used by mammalian cells in response to infection by pathogens. Dev. Genet. 21:279–289, 1997. © 1997 Wiley-Liss, Inc.     

高等植物的PCD研究进展(一)

植物细胞程序性死亡(programmed cell death,PCD)已成为当前生物学的研究热点之一。植物PCD普遍存在于植物器官和个体生长发育过程及与环境相互作用过程中,具有重要的生物学意义。在高等植物生长发育过程中,根冠细胞、导管细胞、绒毡层细胞、胚乳细胞、胚柄细胞、糊粉细胞、大孢子细胞、助细胞和反足细胞等细胞在一定程度上均发生了PCD。另外,衰老也涉及PCD。本文综述了最近几年来与发育有关的PCD研究进展,主要包括高等植物细胞死亡的形式、起因及其PCD的形态、生化特征及高等植物营养器官(根、茎和叶)和生殖器官(花、果实和种子)在其生长发育过程中的PCD。文章最后还对植物PCD的进化和生物学意义作了进一步的讨论。 Abstract：Plant programmed cell death(PCD),the details of which are becoming a focus of intensive research in biology, is a ubiquitous phenomenon and plays an improtant biological role in the develpoment of organs and whole organisms and in interactions with the environment.During higher plant development,root cap cells,tracheary elements(TEs),tapetalcells,endosperm cells,suspensor cells,aleurone cells,megaspore cells,help cells and antipodal cells,etc.undergo PCD to some degree.In addition,senescence also involves PCD.This paper mainly reviewed PCD research progress in higher plant development in recent years,including forms and causes of cell death and PCD morphological and biochemical features in higher plants;PCD in development of nutritive organs(root ,stem and leaf) and reproductive organs(flower ,fruit and seed),evolution and biological rloes of plant PCD were further discussed in the paper.     

Programmed senescence of plant organs

The senescence of plant organs associated with reproductive development has been studied extensively during the past century, and it has long been recognized that this type of death is internally programmed. The regulation of organ senescence as well as its biochemical and genetic determinants has been an historically rich area of research. Certain plant hormones have been implicated as regulators or modulators of organ senescence and many of the biochemical pathways associated with the senescence syndrome have been elucidated. The genetic basis of organ senescence has also been well established by the identification of mutations that impair the senescence program and recently, transgenic plants have been used to critically determine the role of specific enzymes and hormonal signals in mediating programmed senescence of plant organs. Here, we review the current understanding of the processes that regulate leaf, flower and fruit senescence, emphasizing the role that programmed organ senescence plays in the adaptive fitness of plants.     

Plant proteolytic enzymes: possible roles during programmed cell death

Proteolytic enzymes are known to be associated with developmentally programmed cell death during organ senescence and tracheary element differentiation. Recent evidence also links proteinases with some types of pathogen- and stress-induced cell suicide. The precise roles of proteinases in these and other plant programmed cell death processes are not understood, however. To provide a framework for consideration of the importance of proteinases during plant cell suicide, characteristics of the best-known proteinases from plants including subtilisin-type and papain-type enzymes, phytepsins, metalloproteinases and the 26S proteasome are summarized. Examples of serine, cysteine, aspartic, metallo- and threonine proteinases linked to animal programmed cell death are cited and the potential for plant proteinases to act as mediators of signal transduction and as effectors of programmed cell death is discussed.     

Regulating the reapers: activating metacaspases for programmed cell death

Research during the past two decades has revealed that specialized cysteine proteases act as conserved initiators or executioners for programmed cell death (PCD) in eukaryotes. Caspases were first identified as common regulators of PCD in metazoans, whereas the role of metacaspases (MCs) as regulators of cellular suicide in plants has only been shown genetically in the past several years. Together with recent biochemical and molecular characterizations of some of the representative MCs from different model systems, multiple mechanisms that can mediate the post-translational regulation of these proteases are beginning to emerge. Further elucidation of these regulatory pathways and definition of the downstream degradomes targeted by MCs should lead to a better understanding of cell death control in plants, protozoans, and fungi.     

植物发育性细胞程序死亡的发生机制

细胞程序死亡是多细胞生物体在内源发育信号或外源环境信号作用下在特定时间和空间发生的细胞死亡过程, 在植物的生长发育过程中起着重要作用。该文介绍了植物细胞程序死亡类型的几种划分方法、植物发育性细胞程序死亡研究常用的实验体系, 并着重概述有关植物发育性细胞程序死亡发生机制的研究进展。     

Caspase-like protease involvement in the control of plant cell death

Cell death as a highly regulated process has now been recognized to be an important, if not essential, pathway that is ubiquitous in all multicellular eukaryotes. In addition to playing key roles in the morphogenesis and sculpting of the organs to give rise to highly specialized forms and shapes, cell death also participates in the programmed creation of specialized cell types for essential functions such as the selection of B cells in the immune system of mammals and the formation of tracheids in the xylem of vascular plants. Studies of apoptosis, the most well-characterized form of animal programmed cell death, have culminated in the identification of a central tripartite death switch the enzymatic component of which is a conserved family of cysteine proteases called caspases. Studies in invertebrates and other animal models suggest that caspases are conserved regulators of apoptotic cell death in all metazoans. In plant systems, the identities of the main executioners that orchestrate cell death remain elusive. Recent evidence from inhibitor studies and biochemical approaches suggests that caspase-like proteases may also be involved in cell death control in higher plants. Furthermore, the mitochondrion and reactive oxygen species may well constitute a common pathway for cell death activation in both animal and plant cells. Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in eukaryotes.     

Plant autophagy puts the brakes on cell death by controlling salicylic acid signaling

It has long been recognized that autophagy in plants is important for nutrient recycling and plays a critical role in the ability of plants to adapt to environmental extremes such as nutrient deprivation. Recent reverse genetic studies, however, hint at other roles for autophagy, showing that autophagy defects in higher plants result in early senescence and excessive immunity-related programmed cell death (PCD), irrespective of nutrient conditions. Until now, the mechanisms by which cells die in the absence of autophagy were unclear. In our study, using biochemical, pharmacological and genetic approaches, we reveal that excessive salicylic acid (SA) signaling is a major factor in autophagy-defective plant-dependent cell death and that the SA signal can induce autophagy. These findings suggest a novel physiological function for plant autophagy that operates via a negative feedback loop to modulate proper SA signaling.     

Recent advances in understanding of the DNA double-strand break repair machinery of plants

Living cells suffer numerous and varied alterations of their genetic material. Of these, the DNA double-strand break (DSB) is both particularly threatening and common. Double-strand breaks arise from exposure to DNA damaging agents, but also from cell metabolism-in a fortuitous manner during DNA replication or repair of other kinds of lesions and in a programmed manner, for example during meiosis or V(D)J gene rearrangement. Cells possess several overlapping repair pathways to deal with these breaks, generally designated as genetic recombination. Genetic and biochemical studies have provided considerable amounts of data about the proteins involved in recombination processes and their functions within these processes. Although they have long played a key role in building understanding of genetics, relatively little is known at the molecular level of the genetic recombination processes in plants. The use of reverse genetic approaches and the public availability of sequence tagged mutants in Arabidopsis thaliana have led to increasingly rapid progress in this field over recent years. The rapid progress of studies of recombination in plants is obviously not limited to the DSB repair machinery as such and we ask readers to understand that in order to maintain the focus and to rest within a reasonable length, we present only limited discussion of the exciting advances in the of plant meiosis field, which require a full review in their own right . We thus present here an update on recent advances in understanding of the DSB repair machinery of plants, focussing on Arabidopsis and making a particular effort to place these in the context of more general of understanding of these processes.     

Apoptosis and plastic surgery

Apoptosis, or programmed cell death, is a phenomenon that is integral to development and cellular homeostasis. In the last decade, many of the essential molecules and pathways that control this phenomenon have been elucidated. Because apoptosis is involved in almost all physiologic and pathologic processes, the understanding of its regulation has significant clinical ramifications. This article reviews the basic understanding of programmed cell death in terms of the effector molecules and pathways. Areas of interest to plastic surgeons are reviewed as they pertain to apoptosis. These areas include allotransplantation, craniofacial and limb development, flap survival, wound healing, stem cell science, and physiologic aging. These topics have not yet been studied extensively in the context of cell death. In this review article, other related and more comprehensively studied scientific areas are used to extrapolate their relevance to apoptosis. Apoptosis is an increasingly better understood process. With the knowledge of how programmed cell death is controlled, combined with the improved ability to effectively perform genetic manipulation and to design specific chemical approaches, apoptosis is gaining clinical relevance. In the next few years, practical clinical breakthroughs will help the medical community to understand the phenomenon of apoptosis and how it relates to the needs of patients.     

Apoptosis in yeast--mechanisms and benefits to a unicellular organism

Initial observations that the budding yeast Saccharomyces cerevisiae can be induced to undergo a form of cell death exhibiting typical markers of apoptosis has led to the emergence of a thriving new field of research. Since this discovery, a number of conserved pro- and antiapoptotic proteins have been identified in yeast. Indeed, early experiments have successfully validated yeasts as a powerful genetic tool with which to investigate mechanisms of apoptosis. However, we still have little understanding as to why programmes of cell suicide exist in unicellular organisms and how they may be benefit such organisms. Recent research has begun to elucidate pathways that regulate yeast apoptosis in response to environmental stimuli. These reports strengthen the idea that physiologically relevant mechanisms of programmed cell death are present, and that these function as important regulators of yeast cell populations.