Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial function
TL;DR: It is shown that glutamate can induce either early necrosis or delayed apoptosis in cultures of cerebellar granule cells, suggesting that mitochondrial function is a critical factor that determines the mode of neuronal death in excitotoxicity.
About: This article is published in Neuron.The article was published on 1995-10-01 and is currently open access. It has received 1893 citations till now. The article focuses on the topics: Excitotoxicity & Glutamate receptor.
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TL;DR: A major unifying thread of the review is a consideration of how the changes occurring during and after ischemia conspire to produce damaging levels of free radicals and peroxynitrite to activate calpain and other Ca(2+)-driven processes that are damaging, and to initiate the apoptotic process.
Abstract: This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...
2,960 citations
TL;DR: The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria.
Abstract: Both physiological cell death (apoptosis) and, in some cases, accidental cell death (necrosis) involve a two-step process. At a first level, numerous physiological and some pathological stimuli trigger an increase in mitochondrial membrane permeability. The mitochondria release apoptogenic factors through the outer membrane and dissipate the electrochemical gradient of the inner membrane. Mitochondrial permeability transition (PT) involves a dynamic multiprotein complex formed in the contact site between the inner and outer mitochondrial membranes. The PT complex can function as a sensor for stress and damage, as well as for certain signals connected to receptors. Inhibition of PT by pharmacological intervention on mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory oncoprotein Bcl-2 prevents cell death, suggesting that PT is a rate-limiting event of the death process. At a second level, the consequences of mitochondrial dysfunction (collapse of the mitochondrial inner 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) entails a bioenergetic catastrophe culminating in the disruption of plasma membrane integrity (necrosis) and/or the activation of specific apoptogenic proteases (caspases) by mitochondrial proteins that leak into the cytosol (cytochrome c, apoptosis-inducing factor) with secondary endonuclease activation (apoptosis). The relative rate of these two processes (bioenergetic catastrophe versus protease and endonuclease activation) determines whether a cell will undergo primary necrosis or apoptosis. The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria. The fact that mitochondrial events control cell death has major implications for the development of cytoprotective and cytotoxic drugs.
2,034 citations
TL;DR: A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products, and apoptosis in many of these systems is characterized as apoptosis.
Abstract: A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being
1,911 citations
TL;DR: Pulsed ATP/depletion/repletion experiments showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
Abstract: Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP) Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation
1,884 citations
TL;DR: This review focuses on mechanisms and emerging concepts that drive the science of stroke in a therapeutic direction and poses a number of fundamental questions that may generate new directions for research and possibly new treatments that could reduce the impact of this enormous economic and societal burden.
1,562 citations
Cites background from "Glutamate-induced neuronal death: A..."
...Massive calcium influx activates catabolic processes mediated by proteases, lipases, and nucleases (Ankarcrona et al., 1995)....
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References
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TL;DR: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation and is used to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
50,114 citations
"Glutamate-induced neuronal death: A..." refers background in this paper
...Normally, mitochondrial enzymes have the capacity to transform MTT tetrazolium salt into MTT formazan (Mosmann, 1983)....
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TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
Abstract: The term apoptosis is proposed for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations. Its morphological features suggest that it is an active, inherently programmed phenomenon, and it has been shown that it can be initiated or inhibited by a variety of environmental stimuli, both physiological and pathological.The structural changes take place in two discrete stages. The first comprises nuclear and cytoplasmic condensation and breaking up of the cell into a number of membrane-bound, ultrastructurally well-preserved fragments. In the second stage these apoptotic bodies are shed from epithelial-lined surfaces or are taken up by other cells, where they undergo a series of changes resembling in vitro autolysis within phagosomes, and are rapidly degraded by lysosomal enzymes derived from the ingesting cells.Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development. It occurs spontaneously in untreated malignant neoplasms, and participates in at least some types of therapeutically induced tumour regression. It is implicated in both physiological involution and atrophy of various tissues and organs. It can also be triggered by noxious agents, both in the embryo and adult animal.
15,416 citations
"Glutamate-induced neuronal death: A..." refers background in this paper
...In contrast, apoptosis is characterized by cell shrinkage, organelle relocalization and compaction, chromatin condensation, and production of membraneenclosed particles containing intracellular material known as "apoptotic bodies" (Kerr et al., 1972; Wyllie et al., 1980; Arends and Wyllie, 1991)....
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TL;DR: It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
Abstract: Publisher Summary The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis.” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.
7,417 citations
"Glutamate-induced neuronal death: A..." refers background in this paper
..., 1994), volume changes (Thomas and Bell, 1981), and genome fragmentation (Wyllie et al., 1980; Zhivotovsky et ai., 1994a)....
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...The cytoplasmic and nuclear changes observed during apoptosis imply an organized rearrangement of the cell structure involving cytoskeletal modifications (Oberhammer et al., 1994), volume changes (Thomas and Bell, 1981), and genome fragmentation (Wyllie et al., 1980; Zhivotovsky et ai., 1994a)....
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...In contrast, apoptosis is characterized by cell shrinkage, organelle relocalization and compaction, chromatin condensation, and production of membraneenclosed particles containing intracellular material known as "apoptotic bodies" (Kerr et al., 1972; Wyllie et al., 1980; Arends and Wyllie, 1991)....
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4,979 citations
TL;DR: It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease.
Abstract: In near-physiological concentrations, glucocorticoid hormones cause the death of several types of normal and neoplastic lymphoid cell, but the mechanisms involved are unknown. One of the earliest structural changes in the dying cell is widespread chromatin condensation, of the type characteristic of apoptosis, the mode of death frequently observed where cell deletion seems to be 'programmed'. It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease.
4,605 citations
"Glutamate-induced neuronal death: A..." refers background in this paper
...In contrast, apoptosis is characterized by cell shrinkage, organelle relocalization and compaction, chromatin condensation, and production of membraneenclosed particles containing intracellular material known as "apoptotic bodies" (Kerr et al., 1972; Wyllie et al., 1980; Arends and Wyllie, 1991)....
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