scholarly journals Enhancer of Zeste Homolog 2 (EZH2) Contributes to Rod Photoreceptor Death Process in Several Forms of Retinal Degeneration and Its Activity Can Serve as a Biomarker for Therapy Efficacy

2021 ◽  
Vol 22 (17) ◽  
pp. 9331
Author(s):  
Martial Mbefo ◽  
Adeline Berger ◽  
Karine Schouwey ◽  
Xavier Gérard ◽  
Corinne Kostic ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Degeneration ◽  
Gene Mutations ◽  
Cell Number ◽  
Death Process ◽  
Epigenetic Mark ◽  
Specific Cell ◽  
Rod Photoreceptor ◽  
Inherited Retinal Dystrophies ◽  
Cell Death Process

Inherited retinal dystrophies (IRD) are due to various gene mutations. Each mutated gene instigates a specific cell homeostasis disruption, leading to a modification in gene expression and retinal degeneration. We previously demonstrated that the polycomb-repressive complex-1 (PRC1) markedly contributes to the cell death process. To better understand these mechanisms, we herein study the role of PRC2, specifically EZH2, which often initiates the gene inhibition by PRC1. We observed that the epigenetic mark H3K27me3 generated by EZH2 was progressively and strongly expressed in some individual photoreceptors and that the H3K27me3-positive cell number increased before cell death. H3K27me3 accumulation occurs between early (accumulation of cGMP) and late (CDK4 expression) events of retinal degeneration. EZH2 hyperactivity was observed in four recessive and two dominant mouse models of retinal degeneration, as well as two dog models and one IRD patient. Acute pharmacological EZH2 inhibition by intravitreal injection decreased the appearance of H3K27me3 marks and the number of TUNEL-positive cells revealing that EZH2 contributes to the cell death process. Finally, we observed that the absence of the H3K27me3 mark is a biomarker of gene therapy treatment efficacy in XLRPA2 dog model. PRC2 and PRC1 are therefore important actors in the degenerative process of multiple forms of IRD.

scholarly journals Inflammation, necrosis, and the kinase RIP3 are key mediators of AAG-dependent alkylation-induced retinal degeneration

2019 ◽  
Vol 12 (568) ◽  
pp. eaau9216 ◽  
Author(s):  
Mariacarmela Allocca ◽  
Joshua J. Corrigan ◽  
Aprotim Mazumder ◽  
Kimberly R. Fake ◽  
Leona D. Samson
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Retinal Degeneration ◽  
Excision Repair ◽  
Alkylating Agents ◽  
Death Process ◽  
Partial Protection ◽  
Cell Death Process ◽  
Base Excision ◽  
Damage Marker

DNA-alkylating agents are commonly used to kill cancer cells, but the base excision repair (BER) pathway they trigger can also produce toxic intermediates that cause tissue damage, such as retinal degeneration (RD). Apoptosis, a process of programmed cell death, is assumed to be the main mechanism of this alkylation-induced photoreceptor (PR) cell death in RD. Here, we studied the involvement of necroptosis (another programmed cell death process) and inflammation in alkylation-induced RD. Male mice exposed to a methylating agent exhibited a reduced number of PR cell rows, active gliosis, and cytokine induction and macrophage infiltration in the retina. Dying PRs exhibited a necrotic morphology, increased 8-hydroxyguanosine abundance (an oxidative damage marker), and overexpression of the necroptosis-associated genes Rip1 and Rip3. The activity of PARP1, which mediates BER, cell death, and inflammation, was increased in PR cells and associated with the release of proinflammatory chemokine HMGB1 from PR nuclei. Mice lacking the anti-inflammatory cytokine IL-10 exhibited more severe RD, whereas deficiency of RIP3 (also known as RIPK3) conferred partial protection. Female mice were partially protected from alkylation-induced RD, showing reduced necroptosis and inflammation compared to males. PRs in mice lacking the BER-initiating DNA glycosylase AAG did not exhibit alkylation-induced necroptosis or inflammation. Our findings show that AAG-initiated BER at alkylated DNA bases induces sex-dependent RD primarily by triggering necroptosis and activating an inflammatory response that amplifies the original damage and, furthermore, reveal new potential targets to prevent this side effect of chemotherapy.

scholarly journals Correction: PML induces a novel caspase-independent cell death process

10.1038/8706 ◽  
1999 ◽  
Vol 22 (1) ◽  
pp. 115-115 ◽  
Author(s):  
Fredérique Quignon
Keyword(s):  
Cell Death ◽  
Death Process ◽  
Cell Death Process

scholarly journals Production of Prodiginines Is Part of a Programmed Cell Death Process in Streptomyces coelicolor

2018 ◽  
Vol 9 ◽  
Author(s):  
Elodie Tenconi ◽  
Matthew F. Traxler ◽  
Charline Hoebreck ◽  
Gilles P. van Wezel ◽  
Sébastien Rigali
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Streptomyces Coelicolor ◽  
Death Process ◽  
Cell Death Process

Characterization of cell death process in plant cells induced by hipoxia and anoxia

2000 ◽  
Vol 28 (5) ◽  
pp. A372-A372
Author(s):  
E. N. Baranova ◽  
N. V. Kononenko ◽  
T. V. Bragina ◽  
G. M. Grineva ◽  
T. P. Astafurova ◽  
...  
Keyword(s):  
Cell Death ◽  
Plant Cells ◽  
Death Process ◽  
Cell Death Process

Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud

1993 ◽  
Vol 106 (1) ◽  
pp. 201-208 ◽  
Author(s):  
V. Garcia-Martinez ◽  
D. Macias ◽  
Y. Ganan ◽  
J.M. Garcia-Lobo ◽  
M.V. Francia ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dna Fragmentation ◽  
Limb Development ◽  
Light Transmission ◽  
Morphological Changes ◽  
Death Process ◽  
Chondrogenic Potential ◽  
Cell Death Process ◽  
Dying Cells

In this work we have attempted to characterize the programmed cell death process in the chick embryonic interdigital tissue. Interdigital cell death is a prominent phenomenon during limb development and has the role of sculpturing the digits. Morphological changes in the regressing interdigital tissue studied by light, transmission and scanning electron microscopy were correlated with the occurrence of internucleosomal DNA fragmentation, evaluated using agarose gels. Programming of the cell death process was also analyzed by testing the chondrogenic potential of the interdigital mesenchyme, in high density cultures. Our results reveal a progressive loss of the chondrogenic potential of the interdigital mesenchyme, detectable 36 hours before the onset of the degenerative process. Internucleosomal DNA fragmentation was only detected concomitant with the appearance of cells dying with the morphology of apoptosis, but unspecific DNA fragmentation was also present at the same time. This unspecific DNA fragmentation was explained by a precocious activation of the phagocytic removal of the dying cells, confirmed in the tissue sections. From our observations it is suggested that programming of cell death involves changes before endonuclease activation. Further, cell surface changes involved in the phagocytic uptake of the dying cells appear to be as precocious as endonuclease activation.

scholarly journals Oxidative Stress in Cell Death and Cardiovascular Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Xu ◽  
Wei Ding ◽  
Xiaoyu Ji ◽  
Xiang Ao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Death Process ◽  
Ros Production ◽  
Disease Treatment ◽  
Physiological Conditions ◽  
Intracellular Ros ◽  
Cell Death Process ◽  
Molecular Components ◽  
Multiple Signaling

ROS functions as a second messenger and modulates multiple signaling pathways under the physiological conditions. However, excessive intracellular ROS causes damage to the molecular components of the cell, which promotes the pathogenesis of various human diseases. Cardiovascular diseases are serious threats to human health with extremely high rates of morbidity and mortality. Dysregulation of cell death promotes the pathogenesis of cardiovascular diseases and is the clinical target during the disease treatment. Numerous studies show that ROS production is closely linked to the cell death process and promotes the occurrence and development of the cardiovascular diseases. In this review, we summarize the regulation of intracellular ROS, the roles of ROS played in the development of cardiovascular diseases, and the programmed cell death induced by intracellular ROS. We also focus on anti-ROS system and the potential application of anti-ROS strategy in the treatment of cardiovascular diseases.

scholarly journals Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes.

1992 ◽  
Vol 12 (7) ◽  
pp. 3060-3069 ◽  
Author(s):  
D S Ucker ◽  
P S Obermiller ◽  
W Eckhart ◽  
J R Apgar ◽  
N A Berger ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Death Process ◽  
Cell Nuclei ◽  
Calcium Dependent ◽  
Nuclear Envelope Breakdown ◽  
Murine Fibroblast ◽  
Cell Death Process ◽  
Cell Suicide ◽  
Physiological Cell Death

We examined virally transformed murine fibroblast clones as targets for cytotoxic T lymphocyte (CTL)-triggered lysis and genome digestion. Strikingly, while all clones were essentially equivalent in the ability to be lysed, one clone, SV3T3-B2.1, failed to exhibit genome digestion associated with CTL attack. Other aspects of the physiological cell death process, including loss of adhesion and nuclear envelope breakdown (lamin phosphorylation and solubilization), were not altered in this clone. The absence of genome digestion associated with CTL-induced cell death correlated with the absence of endodeoxyribonuclease activity in the nuclei of that clone. Characterization of the activity affected identifies a calcium-dependent, DNase I-like endonuclease of approximately 40 kDa, normally present constitutively in all cell nuclei, as the enzyme responsible for genome digestion associated with CTL-mediated cell death. These observations indicate that neither genome digestion per se nor its consequences [such as activation of poly(ADP-ribose) polymerase] are essential for cell death resulting from the triggering of this cell suicide process.

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