Radiation-induced astrocyte senescence is rescued by del133p53

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Radiation-induced astrocyte senescence is rescued by del133p53

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Radiation-induced astrocyte senescence is rescued by del133p53

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Neuro oncology

ISSN

1522-8517

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

474-485

Kód UT WoS článku

000462632100008

EID výsledku v databázi Scopus

2-s2.0-85063277119