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Epigenetic Control of Apoptosis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 1405

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Guest Editor
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA
Interests: apoptosis; epigenetics; DNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the enormous progress made since apoptosis rediscovery in the second half of the last century, our understanding of the regulatory mechanisms essential to maintain the balance between cell survival and death continues to evolve. Recent advances include epigenetic modifications involved in the imbalance of apoptotic pathways and apoptosis targeting epigenetic modulators explored for reversing such dysregulation.

In this Special Issue, we aim to collect high-quality research papers and reviews on the effects of DNA methylation, histone modifications, and non-coding RNAs on various mechanisms of apoptotic pathways, including regulated DNA fragmentation and chromatin condensation.

Dr. Tetiana Zaǐchuk
Guest Editor

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Keywords

  • apoptosis
  • epigenetics
  • gene expression
  • DNA and histone modifications
  • non-coding RNAs
  • chromatin
  • signal transduction

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Published Papers (1 paper)

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Research

21 pages, 2580 KiB  
Article
p53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells
by Kealan McElhinney, Mustapha Irnaten, Jeffrey O’Callaghan and Colm O’Brien
Int. J. Mol. Sci. 2024, 25(22), 12173; https://doi.org/10.3390/ijms252212173 - 13 Nov 2024
Viewed by 924
Abstract
Lamina cribrosa (LC) cells play an integral role in extracellular matrix remodeling and fibrosis in human glaucoma. LC cells bear similarities to myofibroblasts that adopt an apoptotic-resistant, proliferative phenotype, a process linked to dysregulation of tumor suppressor-gene p53 pathways, including ubiquitin-proteasomal degradation via [...] Read more.
Lamina cribrosa (LC) cells play an integral role in extracellular matrix remodeling and fibrosis in human glaucoma. LC cells bear similarities to myofibroblasts that adopt an apoptotic-resistant, proliferative phenotype, a process linked to dysregulation of tumor suppressor-gene p53 pathways, including ubiquitin-proteasomal degradation via murine-double-minute-2 (MDM2). Here, we investigate p53 and MDM2 in glaucomatous LC cells. Primary human LC cells were isolated from glaucomatous donor eyes (GLC) and age-matched normal controls (NLC) (n = 3 donors/group). LC cells were cultured under standard conditions ± 48-h treatment with p53-MDM2-interaction inhibitor RG-7112. Markers of p53-MDM2, fibrosis, and apoptosis were analyzed by real-time polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence. Cellular proliferation and viability were assessed using colorimetric methyl-thiazolyl-tetrazolium salt assays (MTS/MTT). In GLC versus NLC cells, protein expression of p53 was significantly decreased (p < 0.05), MDM2 was significantly increased, and immunofluorescence showed reduced p53 and increased MDM2 expression in GLC nuclei. RG-7112 treatment significantly increased p53 and significantly decreased MDM2 gene and protein expression. GLC cells had significantly increased protein expression of αSMA, significantly decreased caspase-3 protein expression, and significantly increased proliferation after 96 h. RG-7112 treatment significantly decreased COL1A1 and αSMA, significantly increased BAX and caspase-3 gene expression, and significantly decreased proliferation in GLC cells. MTT-assay showed equivocal cellular viability in NLC/GLC cells with/without RG-7112 treatment. Our data suggests that proliferation and the ubiquitin-proteasomal pathway are dysregulated in GLC cells, with MDM2-led p53 protein degradation negatively impacting its protective role. Full article
(This article belongs to the Special Issue Epigenetic Control of Apoptosis)
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