Hypersensitive response-related death

The hypersensitive response (HR) of plants resistant to microbial pathogens involves a complex form of programmed cell death (PCD) that differs from developmental PCD in its consistent association with the induction of local and systemic defence responses. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen avirulence gene products and those of plant resistance genes and it can be the result of multiple signalling pathways. Ion fluxes and the generation of reactive oxygen species commonly precede cell death, but a direct involvement of the latter seems to vary with the plant-pathogen combination. Protein synthesis, an intact actin cytoskeleton and salicylic acid also seem necessary for cell death induction. Cytological studies suggest that the actual mode and sequence of dismantling the cell contents varies among plant-parasite systems although there may be a universal involvement of cysteine proteases. It seems likely that cell death within the HR acts more as a signal to the rest of the plant rather than as a direct defence mechanism.     

Mitochondrial permeability transition in apoptosis and necrosis

Apoptosis has classically been viewed as a process not involving mitochondria, whereas the implication of mitochondrial dysfunction in necrosis has been recognized for several decades. Recently, it has become clear that apoptosis implies a disruption of mitochondrial membrane intregrity that is decisive for the cell death process. Cytofluorometric methods assessing the mitochondrial membrane function and structure can be employed to demonstrate that, at least in most models of apoptosis, mitochondrial changes precede caspase and nuclease activation. Moreover, pharmacological and genetic experiments suggest that the loss of mitochondrial membrane integrity is a critical event of the apoptotic process, beyond or at the point of no return of programmed cell death. Inhibitors of the mitochondrial megachannel (= permeability transition pore) can prevent both the mitochondrial and the post-mitochondrial manifestations of apoptosis.     

植物细胞程序性死亡中的类胱天蛋白酶研究进展

胱天蛋白酶(caspases)在动物细胞程序性死亡(programmed cell death,PCD)的起始、执行以及信号转导阶段起着关键作用,目前在植物中也发现有类胱天蛋白酶(caspase-like proteases,CLPs)的存在,并确认液泡加工酶(VPEs)、metacaspases和丝氨酸内肽酶(sapases)具有CLPs的作用,并证实CLPs参与植物的生长发育、抗病性及胁迫诱导的细胞程序性死亡等.本文对植物CLPs活性、生化结构及生理作用等方面的研究进展进行综述,并与动物caspases进行比较,为今后CLPs活性调节、作用方式及其在植物细胞程序性死亡中的作用等方面的研究提供参考.     

Mitochondrial Implication in Accidental and Programmed Cell Death: Apoptosis and Necrosis

Both physiological cell death (apoptosis) and at least some cases of accidental cell death (necrosis) involve a two-step-process. At a first level, numerous physiological or pathological stimuli can trigger mitochondrial permeability transition which constitutes a rate-limiting event and initiates the common phase of the death process. Mitochondrial permeability transition (FT) involves the formation of proteaceous, regulated pores, probably by apposition of inner and outer mitochondrial membrane proteins which cooperate to form the mitochondrial PT pore complex. Inhibition of PT by pharmacological intervention on mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory oncoprotein Bcl-2 thus can prevent cell death. At a second level, the consequences of mitochondrial dysfunction (collapse of the mitochondrial transmembrane potential, uncoupling of the respiratory chain, hyperproduction of superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix calcium and glutathione, and release of soluble intermembrane proteins) can entail a bioenergetic catastrophe culminating in the disruption of plasma membrane integrity (necrosis) and/or the activation and action of apoptogenic proteases with secondary endonuclease activation and consequent oligonucleosomal DNA fragmentation (apoptosis). The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from the mitochondrial intermembrane space. This scenario applies to very different models of cell death. The notion that mitochondrial events control cell death has major implications for the development of death-inhibitory drugs.     

植物细胞程序性死亡──一个新兴的研究领域(英文)

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（ＰｒｏｇｒａｍｍｅｄＣｅｌｌＤｅａｔｈ,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基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。尽管已证明一些信号分子如活性氧种     

What happened to plant caspases?

The extent of conservation in the programmed cell death pathways that are activated in species belonging to different kingdoms is not clear. Caspases are key components of animal apoptosis; caspase activities are detected in both animal and plant cells. Yet, while animals have caspase genes, plants do not have orthologous sequences in their genomes. It is 10 years since the first caspase activity was reported in plants, and there are now at least eight caspase activities that have been measured in plant extracts using caspase substrates. Various caspase inhibitors can block many forms of plant programmed cell death, suggesting that caspase-like activities are required for completion of the process. Since plant metacaspases do not have caspase activities, a major challenge is to identify the plant proteases that are responsible for the caspase-like activities and to understand how they relate, if at all, to animal caspases. The protease vacuolar processing enzyme, a legumain, is responsible for the cleavage of caspase-1 synthetic substrate in plant extracts. Saspase, a serine protease, cleaves caspase-8 and some caspase-6 synthetic substrates. Possible scenarios that could explain why plants have caspase activities without caspases are discussed.     

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.     

胱冬肽酶非依赖性的细胞程序性死亡

在多细胞有机体的组织内稳态维持和正常发育过程中,细胞程序性死亡发挥着重要的作用。细胞程序性死亡有多种形式(如细胞凋亡、类细胞凋亡和类坏死等),其中了解较清楚的是细胞凋亡。一直以来,胱冬肽酶(caspase)被认为是细胞凋亡发生中关键的一种蛋白酶。但是最近的研究表明,包括细胞凋亡在内的一些细胞程序性死亡可以以一种不依赖胱冬肽酶的方式发生。细胞程序性死亡与胱冬肽酶之间存在非依赖性关系。     

Phytaspase,a relocalisable cell death promoting plant protease with caspase specificity

Caspases are cysteine‐dependent proteases and are important components of animal apoptosis. They introduce specific breaks after aspartate residues in a number of cellular proteins mediating programmed cell death (PCD). Plants encode only distant homologues of caspases, the metacaspases that are involved in PCD, but do not possess caspase‐specific proteolytic activity. Nevertheless, plants do display caspase‐like activities indicating that enzymes structurally distinct from classical caspases may operate as caspase‐like proteases. Here, we report the identification and characterisation of a novel PCD‐related subtilisin‐like protease from tobacco and rice named phytaspase (plant aspartate‐specific protease) that possesses caspase specificity distinct from that of other known caspase‐like proteases. We provide evidence that phytaspase is synthesised as a proenzyme, which is autocatalytically processed to generate the mature enzyme. Overexpression and silencing of the phytaspase gene showed that phytaspase is essential for PCD‐related responses to tobacco mosaic virus and abiotic stresses. Phytaspase is constitutively secreted into the apoplast before PCD, but unexpectedly is re‐imported into the cell during PCD providing insights into how phytaspase operates.     

Demonstration of motoneuron-12 sparing in cultured Manduca sexta ventral nerve cords

The emergence of the adult Manduca sexta moth is accompained by the death of half of the neurons present in the pupal abdominal nervous system (Truman, 1983). This developmental neuronal death is highly selective, so that the same neurons die at the same time relative to emergence in every moth. In the case of the MN-12 motoneurons, this cell death is regulated both by hemolymph concentrations of a steroid hormone, 20-hydroxyecdysone, and by actions exerted by adjacent ganglia (Truman and Schwartz, 1984; Fahrbach and Truman, 1987). This latter effect, which has been previously described in isolated abdomens and in moths with transected ventral nerve cords, has now been reproduced under controlled culture conditions in which the selectivity and extent of postemergence neuronal death is comparable to that seen in vivo. With respect to the MN-12 neurons found in the most anterior unfused abdominal ganglion, A₃, the pterothoracic ganglion appears to be the source of a factor that permits these neurons to die according to their usual developmental schedule. © 1992 John Wiley & Sons, Inc.     

Proteolytic enzyme activities in Cheddar cheese juice made using lactococcal starters of differing autolytic properties

AIMS: To determine proteolytic enzyme activities released in Cheddar cheese juice manufactured using lactococcal starter strains of differing autolytic properties. METHODS AND RESULTS: The activities of residual chymosin, cell envelope proteinase and a range of intracellular proteolytic enzymes were determined during the first 70 days of ripening when starter lactococci predominate the microbial flora. In general, in cell free extracts (CFE) of the strains, the majority of proteolytic activities was highest for Lactococcus lactis HP, intermediate for L. lactis AM2 and lowest for L. lactis 303. However, in cheese juice, as ripening progressed, released proteolytic activities were highest for the highly autolytic strain L. lactis AM2, intermediate for L. lactis 303 and lowest for L. lactis HP. CONCLUSIONS: These results indicate that strain related differences in autolysis influence proteolytic enzyme activities released into Cheddar cheese during ripening. No correlation was found between proteolytic potential of the starter strains measured in CFE prior to cheese manufacture and levels of activities released in cheese juice. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings further support the importance of autolysis of lactococcal starters in determining the levels of proteolytic activities present in cheese during initial stages of ripening.     

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。     

The non‐existent aging program: how does it work?

Summary Aging and lifespan determination have been viewed, in the most well-accepted theories, as nonprogrammatic, and are thought to result from the evolutionary selection for early fitness at the expense of late survival. Here, recent data implicating potentially programmatic aspects of aging and lifespan determination are discussed, and analogies between programmed cell death and programmed organismal death are offered. It is hoped that the recognition of at least the possibility of a programmatic aspect, or aspects, to the determination of longevity and the process of aging will help to optimize our chances to identify appropriate therapeutic targets both for longevity enhancement and disease prevention.     

Cloning and sequencing of a cDNA encoding the rat Bcl-2 protein

A rat cDNA encoding the Bcl-2 protein was cloned and sequenced. The primary amino-acid sequence deduced from the nucleotide sequence reveals a 236-aa protein having extensive homology with the mouse (95%), human (87%) and chicken (71%) Bcl-2 proteins.