Radiation-induced astrocyte senescence is rescued by del133p53

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F19%3A00078132" target="_blank" >RIV/00209805:_____/19:00078132 - isvavai.cz</a>

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=30615147" target="_blank" >https://www.ncbi.nlm.nih.gov/pubmed/?term=30615147</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/neuonc/noz001" target="_blank" >10.1093/neuonc/noz001</a>

Result language

angličtina

Original language name

Radiation-induced astrocyte senescence is rescued by del133p53

Original language description

Cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to the development of radiation therapy-associated side effects in the lung and blood vessels by promoting chronic inflammation. In the brain, inflammation contributes to the development of neurologic disease including Alzheimer&apos;s disease. In this study, we investigated the roles of cellular senescence and 133p53, an inhibitory isoform of p53, in radiation-induced brain injury. METHODS: Senescent cell types in irradiated human brain were identified with immunohistochemical labeling of senescence-associated proteins, p16 INK4A and heterochromatin protein, Hp1gama, in 13 patient cases including 7 irradiated samples. To investigate the impact of radiation on astrocytes specifically, primary human astrocytes were irradiated and examined for expression of del133p53 and induction of SASP. Lentiviral expression of del133p53 was performed to investigate its role in regulating radiation-induced cellular senescence and astrocyte-mediated neuroinflammation. RESULTS: Astrocytes expressing p16INK4A and Hp1gamma were identified in all irradiated tissues, were increased in number in irradiated compared to untreated cancer patient tissues and had higher labeling intensity in irradiated tissues compared to age-matched controls. Human astrocytes irradiated in vitro also experience induction of cellular senescence, have diminished del133p53 and adopt a neurotoxic phenotype as demonstrated by increased senescence-associated beta-galactosidase activity, p16INK4A, and IL-6. In human astrocytes, del133p53 inhibits radiation-induced senescence, promotes DNA double-strand break repair, and prevents astrocyte-mediated neuroinflammation and neurotoxicity. CONCLUSIONS: Restoring expression of the endogenous p53 isoform, del133p53, protects astrocytes from radiation-induced senescence, promotes DNA repair, and inhibits astrocyte-mediated neuroinflammation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neuro oncology

ISSN

1522-8517

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

474-485

UT code for WoS article

000462632100008

EID of the result in the Scopus database

2-s2.0-85063277119