AMPA-Induced Excitotoxicity Increases Nuclear Levels of CAD, Endonuclease G, and Acinus and Induces Chromatin Condensation in Rat Hippocampal Pyramidal Neurons

Henne, W.; Oomman, Sowmini; Attridge, Jennifer; Coates, Philip J.; Bliss, Richard; Strahlendorf, Howard K.; Strahlendorf, Jean C.

doi:10.1007/s10571-006-9031-2

Cited by 6 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until recently, the role of Endo G in PCD has been unclear, due to conflicting reports on its significance in apoptosis [107][108][109]. In neurones Endo G translocates to the nucleus during cell death, although it is uncertain whether it is active in these systems [28,110,111]. Recently, Endo G was shown to be required for PCD-Type III in cortical neurons under oxidative stress on the basis of siRNA-mediated down regulation of Endo G [27].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Multifaceted deaths orchestrated by mitochondria in neurones

Nagley

Higgins

Atkin

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Neurones undergo diverse forms of cell death depending on the nature and severity of the stress. These death outcomes are now classified into various types of programmed cell death, including apoptosis, autophagy and necrosis. Each of these pathways can run in parallel and all have mitochondria as a central feature. Recruitment of mitochondria into cell death signalling involves either (or both) induction of specific death responses through release of apoptogenic proteins into the cytosol, or perturbation in function leading to loss of mitochondrial energisation and ATP synthesis. Cross-talk between these signalling pathways, particularly downstream of mitochondria, determines the resultant pattern of cell death. The differential recruitment of specific death pathways depends on the timing of engagement of mitochondrial signalling. Other influences on programmed cell death pathways occur through stress of the endoplasmic reticulum and the associated ubiquitin-proteasome system normally handling potentially neurotoxic protein aggregates. Based upon contemporary evidence apoptosis is a relatively rare in the mature brain whereas the contribution of programmed necrosis to various neuropathologies has been underestimated. The death outcomes that neurones exhibit during acute or chronic injury or pathological conditions considered here (oxidative stress, hypoxic-ischaemic injury, amyotrophic lateral sclerosis, Parkinson's and Huntington's diseases) fall within a spectrum of the diverse death types across the apoptosis-necrosis continuum. Indeed, dying or dead neurones cells may simultaneously manifest characteristics of more than one of death pathway. Understanding neuronal death pathways and their cross-talk not only informs the detailed pathobiology but also suggests novel therapeutic strategies.

show abstract

Section: Accepted M Manuscriptmentioning

confidence: 99%

Multifaceted deaths orchestrated by mitochondria in neurones

Nagley

Higgins

Atkin

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

show abstract

“…Similarly, endonuclease G (endoG) is a caspase-independent nuclease found in mitochondria (Li et al, 2001), and during apoptosis, is released from the mitochondria and cleaves chromatin DNA within the nucleus (Li et al, 2001). Previous research has indicated that levels of endoG rise following AMPA-induced excitotoxicity (Henne et al, 2006), an effect which may generalize to all glutamate-induced excitotoxicity. Thus, the time-dependent decline of NMDA-induced PI fluorescence likely reflects catabolic processes initiated by Ca 2+ -dependent signaling with NMDA exposure.…”

Section: Discussionmentioning

confidence: 99%

Temporal dependence of cysteine protease activation following excitotoxic hippocampal injury

Berry¹,

Sharrett-Field²,

Butler³

et al. 2012

Neuroscience

View full text Add to dashboard Cite

Excitotoxic insults can lead to intracellular signaling cascades that contribute to cell death, in part by activation of proteases, phospholipases, and endonucleases. Cysteine proteases, such as calpains, are calcium-activated enzymes which degrade cytoskeletal proteins, including microtubule-associated proteins, tubulin, and spectrin, among others. The current study used the organotypic hippocampal slice culture model to examine whether pharmacologic inhibition of cysteine protease activity inhibits N-methyl-D-aspartate- (NMDA-) induced excitotoxic (20 μM NMDA) cell death and changes in synaptophysin immunoreactivity. Significant NMDA-induced cytotoxicity (as measured by propidium iodide [PI] uptake) was found in the CA1 region of the hippocampus at all timepoints examined (24, 72, 120 hours), an effect significantly attenuated by co-exposure to the selective NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV), but not MDL-28170, a potent cysteine protease inhibitor. Results indicated sparing of NMDA-induced loss of the synaptic vesicular protein synaptophysin in all regions of the hippocampus by MDL-28170, though only at early timepoints after injury. These results suggest calcium-dependent recruitment of cysteine proteases within 24 hours of excitotoxic insult, but activation of alternative cellular degrading mechanisms after 24 hours. Further, these data suggest that synaptophysin may be a substrate for calpains and related proteases.

show abstract

“…RhCNTF was given at the start of reoxygenation phase. 3) Method to Analysis Image: According to the injury and the treatments of different concentrations of rhCNTF, neurons were observed by using both optics and fluorescent imaging to obtain morphological evidence for neurite length and nuclear condensation/aggregation [7] under inverted phase contrast microscope, respectively. Cultured cortical neurons were visualized by immunocytochemistry with a monoclonal mouse antibody (TuJ1) against the neuronal marker β-III tubulin.…”

Section: Evaluation Of Rhcntf In Cortical Neurons Subjected To Ogd/rmentioning

confidence: 99%

Recombinant Human Ciliary Neurotrophic Factor Protects MCAO/R Rat Brain against Neuronal Degeneration and Apoptosis by Regulating NOS Expression

Liu

Zhang

Chen

et al. 2013

AMR

View full text Add to dashboard Cite

To research the effects and mechanisms of recombinant human ciliary neurotrophic factor (rhCNTF) on ischemia/reperfusion in vivo and in vitro, rhCNTF was biosynthesized, and ischemia/reperfusion-like models were used. Protection by rhCNTF was studied at the in vivo level using a model of middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. RhCNTF was administrated just before reperfusion. RhCNTF markedly increased animal viability, decreased infarct volumes and neurological deficit scores. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation/reoxygenation, and treated with rhCNTF prophylactically. Results indicated that neuronal survival rates were increased, LDH release was decreased and lose of neurite length were alleviated in rhCNTF group, and this protection was associated with nerotrophic effect, nitric oxide and neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS). The data suggest that rhCNTF may be a good therapeutic reagent to reduce cerebral ischemia/reperfusion injury, and may act by NOS regulation.

show abstract

AMPA-Induced Excitotoxicity Increases Nuclear Levels of CAD, Endonuclease G, and Acinus and Induces Chromatin Condensation in Rat Hippocampal Pyramidal Neurons

Cited by 6 publications

References 22 publications

Multifaceted deaths orchestrated by mitochondria in neurones

Multifaceted deaths orchestrated by mitochondria in neurones

Temporal dependence of cysteine protease activation following excitotoxic hippocampal injury

Recombinant Human Ciliary Neurotrophic Factor Protects MCAO/R Rat Brain against Neuronal Degeneration and Apoptosis by Regulating NOS Expression

Contact Info

Product

Resources

About