Journal ArticleDOI
Oxidative stress induces apoptosis in embryonic cortical neurons.
TLDR
It is found that glutathione depletion leads to hypercondensation and fragmentation of chromatin into spherical or irregular shapes, a morphologic signature of apoptosis, which suggests that oxidative stress can induce apoptosis in neurons.Abstract:
Glutamate-induced glutathione depletion in immature embryonic cortical neurons has been shown to lead to oxidative stress and cell death. We have used this in vitro model to investigate the mechanism(s) by which free radicals induce neuronal degeneration. We find that glutathione depletion leads to hyper-condensation and fragmentation of chromatin into spherical or irregular shapes, a morphologic signature of apoptosis. These morphologic changes are accompanied by laddering of DNA into multiple oligonucleosomal fragments and can be prevented by the antioxidants idebenone and butylated hydroxyanisole. Cell death induced by glutathione depletion can also be prevented by inhibitors of macromolecular synthesis. Taken together, these observations suggest that oxidative stress can induce apoptosis in neurons.read more
Citations
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Journal ArticleDOI
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
Journal ArticleDOI
Oxidative stress, glutamate, and neurodegenerative disorders
TL;DR: Two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
Journal ArticleDOI
Reactive oxygen species and programmed cell death
TL;DR: Three recent papers indicate that ROS are not required for PCD and that Bcl-2 can protect against cell death even under conditions where ROS are unlikely to be produced.
Journal ArticleDOI
Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro.
TL;DR: Since extremely poor semen samples are the indication for intracytoplasmic sperm injection, there is a high likelihood that sperm with fragmented DNA may be selected by chance and used for oocyte injection, resulting in poor fertilization and/or cleavage rates.
Journal ArticleDOI
Neurodegeneration in Excitotoxicity, Global Cerebral Ischemia, and Target Deprivation: A Perspective on the Contributions of Apoptosis and Necrosis
Lee J. Martin,Nael A. Al-Abdulla,Ansgar M. Brambrink,Jeffrey R. Kirsch,Frederick E. Sieber,Carlos Portera-Cailliau +5 more
TL;DR: It is found that N-methyl-D-aspartate (NMDA) receptor- and non-NMDA receptor-mediated excitotoxic injury results in neurodegeneration along an apoptosis-necrosis continuum, in which neuronal death is influenced by the degree of brain maturity and the subtype of glutamate receptor that is stimulated.
References
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Book ChapterDOI
Cell death : the significance of apoptosis
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.
Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
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.
Journal ArticleDOI
Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress
TL;DR: Glutamate-induced cytotoxicity in N18-RE-105 cells is due to inhibition of cystine uptake, resulting in lowered glutathione levels leading to oxidative stress and cell death.
Journal ArticleDOI
Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation.
David P. Martin,Robert E. Schmidt,P S DiStefano,Oliver H. Lowry,Joyce G. Carter,Eugene M. Johnson +5 more
TL;DR: The fact that sympathetic neurons must synthesize protein and RNA to die when deprived of NGF indicates that NGF, and presumably other neurotrophic factors, maintains neuronal survival by suppressing an endogenous, active death program.