scholarly journals Investigating the Relationship Between Neuronal Cell Death and Early DNA Methylation After Ischemic Injury

2020 ◽  
Vol 14 ◽  
Author(s):  
Mayumi Asada ◽  
Hideki Hayashi ◽  
Kenjiro Murakami ◽  
Kento Kikuiri ◽  
Ryotaro Kaneko ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
The Relationship

scholarly journals Roles of DNA methylation in neuronal cell death after ischemic injury

2021 ◽  
Vol 94 (0) ◽  
pp. 1-O-C1-3
Author(s):  
Mayumi Asada ◽  
Hideki Hayashi ◽  
Kenjiro Murakami ◽  
Kento Kikuiri ◽  
Ryotaro Kaneko ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury

Abstract 2505: Neuronal-specific Loss of p53 Function in Forebrain Neurons is Protective Against Ischemic Injury

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Yu Luo ◽  
Hui Shen ◽  
Barry Hoffer
Keyword(s):  
Cell Death ◽  
P53 Protein ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
P53 Gene ◽  
Brain Regions ◽  
Abnormal Development ◽  
Significant Advance ◽  
Forebrain Neurons

The p53 gene is a key regulator of cell apoptosis. It has been suggested that p53 function is involved in cell death in stroke. p53 immunoreactivity has been detected in brain tissue derived from animal models of stroke. Pharmacological inhibition of p53 function leads to decreased ischemic damage in animal stroke models. In addition, a recent study has reported that the human Tp53 Arg72Pro polymorphism correlates with different functional prognosis in stroke patients. However, both the pharmacological inhibitor and genetic linkage studies do not address the question whether p53 function determines the outcome of stroke by directly regulating cell death in neurons. To address this question, we investigated the role of p53 in ischemia-induced neuronal cell death using forebrain neuron-specific ablation of the gene coding for the p53 gene in mice. By expressing Cre recombinase under the control of the Camkinase II promoter, we achieved a selective deletion of functional p53 protein in forebrain neurons. This strategy represents a significant advance because it permits an evaluation of p53 function in these specific cells, compared to non-selective effects of pharmacological inhibitors on multiple cell types in multiple anatomical regions. Effectiveness of specific p53 deletion in forebrain, but no other brain regions and other organs, was confirmed by PCR in Camkinase II -cre/LoxP p53 ko mice. Loss of the p53 gene in forebrain neurons did not lead to abnormal development of the cortex, as demonstrated by normal structure of the forebrain and neuronal cell numbers (NeuN positive cells) in ko mice. This suggests that p53 is not involved in the apoptosis which eliminates excess neurons during development. However, we found that loss of p53 in forebrain neurons in adult mice is protective against ischemic injury after stroke (MCAo). Locomotor behavior measured in automated activity chambers showed that Camkinase II -cre/LoxP p53 ko mice have less locomotor deficits compared to wt mice after MCAo. Therefore, our data suggest that loss of p53 function specifically in forebrain neurons can protect these cells from ischemic injury occurring after stroke and neuronal-specific inhibition of p53 might be a new treatment strategy for improved prognosis.

scholarly journals Nuclear Factor of Activated T Cells 5 Deficiency Increases the Severity of Neuronal Cell Death in Ischemic Injury

Neurosignals ◽  
2012 ◽  
Author(s):  
Keri Man Chi Mak ◽  
Amy Cheuk Yin Lo ◽  
Amy Ka Man Lam ◽  
Patrick Ka Kit Yeung ◽  
Ben Chi Bun Ko ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
Nuclear Factor ◽  
Activated T Cells

scholarly journals Programmed Cell Death in Cerebral Ischemia

2001 ◽  
Vol 21 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Steven H. Graham ◽  
Jun Chen
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Programmed Cell Death ◽  
Viral Vector ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
Morphologic Change ◽  
Altered Expression ◽  
Ischemic Brain

Programmed cell death (PCD) is an ordered and tightly controlled set of changes in gene expression and protein activity that results in neuronal cell death during brain development. This article reviews the molecular pathways by which PCD is executed in mammalian cells and the potential relation of these pathways to pathologic neuronal cell death. Whereas the classical patterns of apoptotic morphologic change often do not appear in the brain after ischemia, there is emerging biochemical and pharmacologic evidence suggesting a role for PCD in ischemic brain injury. The most convincing evidence for the induction of PCD after ischemia includes the altered expression and activity in the ischemic brain of deduced key death-regulatory genes. Furthermore, studies have shown that alterations in the activity of these gene products by peptide inhibitors, viral vector-mediated gene transfer, antisense oligonucleotides, or transgenic mouse techniques determine, at least in part, whether ischemic neurons live or die after stroke. These studies provide strong support for the hypothesis that PCD contributes to neuronal cell death caused by ischemic injury. However, many questions remain regarding the precise pathways that initiate, sense, and transmit cell death signals in ischemic neurons and the molecular mechanisms by which neuronal cell death is executed at different stages of ischemic injury. Elucidation of these pathways and mechanisms may lead to the development of novel therapeutic strategies for brain injury after stroke and related neurologic disorders.

scholarly journals Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

2017 ◽  
Vol 43 (1) ◽  
pp. 182-194 ◽  
Author(s):  
Dong Guo ◽  
Ji Ma ◽  
Lei Yan ◽  
Tengfei Li ◽  
Zhiguo Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Injury ◽  
Down Regulation ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Background/Aims: LncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be highly expressed in an in vitro mimic of ischemic stroke conditions. However, the exact biological role of MALAT1 and its underlying mechanism in ischemic stroke remain to be elucidated. Methods: The roles of MALAT1 and miR-30a on cell death and infarct volume and autophagy were evaluated in experimental ischemic stroke. The relationships between miR-30a and MALAT1, Beclin1 were confirmed by luciferase reporter assay. The autophagy inhibitor 3-methyadenine (3-MA) was used to examine the impact of autophagy on ischemic injury. Results: We found that MALAT1, along with the levels of conversion from autophagy-related protein microtubule-associated protein light chain 3-I (LC3-I) to LC3-phosphatidylethanolamine conjugate (LC3-II), as well as Beclin1 were up-regulated and miR-30a was down-regulated in cerebral cortex neurons after oxygen-glucose deprivation (OGD) and mouse brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Down-regulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo. Furthermore, MALAT1 may serve as a molecular sponge for miR-30a and negatively regulate its expression. In addition, MALAT1 overturned the inhibitory effect of miR-30a on ischemic injury and autophagy in vitro and in vivo, which might be involved in the derepression of Beclin1, a direct target of miR-30a. Mechanistic analyses further revealed that autophagy inhibitor 3-methyadenine (3-MA) markedly suppressed OGD-induced neuronal cell death and MCAO-induced ischemic brain infarction. Conclusion: Taken together, our study first revealed that down-regulation of MALAT1 attenuated neuronal cell death through suppressing Beclin1-dependent autophagy by regulating miR-30a expression in cerebral ischemic stroke. Besides, our study demonstrated a novel lncRNA-miRNA-mRNA regulatory network that is MALAT1-miR-30a-Beclin1 in ischemic stroke, contributing to a better understanding the pathogenesis and progression of ischemic stroke.

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