-
Je něco špatně v tomto záznamu ?
Radiation-induced astrocyte senescence is rescued by Δ133p53
C. Turnquist, JA. Beck, I. Horikawa, IE. Obiorah, N. Von Muhlinen, B. Vojtesek, DP. Lane, C. Grunseich, JJ. Chahine, HM. Ames, DD. Smart, BT. Harris, CC. Harris,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
PubMed Central od 1999 do Před 1 rokem
Europe PubMed Central od 1999 do Před 1 rokem
Open Access Digital Library od 1999-01-01
Medline Complete (EBSCOhost) od 2004-01-01 do Před 1 rokem
Odkazy
PubMed
30615147
DOI
10.1093/neuonc/noz001
Knihovny.cz E-zdroje
- MeSH
- astrocyty metabolismus účinky záření MeSH
- kraniální ozáření škodlivé účinky MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nádory mozku radioterapie MeSH
- protein - isoformy metabolismus MeSH
- radiační poranění metabolismus MeSH
- stárnutí buněk účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Cellular senescence and the senescence-associated secretory phenotype (SASP) may 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's disease. In this study, we investigated the roles of cellular senescence and Δ133p53, 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 p16INK4A and heterochromatin protein Hp1γ 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 Δ133p53 and induction of SASP. Lentiviral expression of ∆133p53 was performed to investigate its role in regulating radiation-induced cellular senescence and astrocyte-mediated neuroinflammation. RESULTS: Astrocytes expressing p16INK4A and Hp1γ were identified in all irradiated tissues, were increased in number in irradiated compared with untreated cancer patient tissues, and had higher labeling intensity in irradiated tissues compared with age-matched controls. Human astrocytes irradiated in vitro also experience induction of cellular senescence, have diminished Δ133p53, and adopt a neurotoxic phenotype as demonstrated by increased senescence-associated beta-galactosidase activity, p16INK4A, and interleukin (IL)-6. In human astrocytes, Δ133p53 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, ∆133p53, protects astrocytes from radiation-induced senescence, promotes DNA repair, and inhibits astrocyte-mediated neuroinflammation.
Department of Pathology Georgetown University Medical Center Washington DC USA
p53 Laboratory Biomedical Sciences Institutes Singapore
Regional Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute Brno Czech Republic
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20022838
- 003
- CZ-PrNML
- 005
- 20201214124849.0
- 007
- ta
- 008
- 201125s2019 xxk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1093/neuonc/noz001 $2 doi
- 035 __
- $a (PubMed)30615147
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxk
- 100 1_
- $a Turnquist, Casmir $u Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 245 10
- $a Radiation-induced astrocyte senescence is rescued by Δ133p53 / $c C. Turnquist, JA. Beck, I. Horikawa, IE. Obiorah, N. Von Muhlinen, B. Vojtesek, DP. Lane, C. Grunseich, JJ. Chahine, HM. Ames, DD. Smart, BT. Harris, CC. Harris,
- 520 9_
- $a BACKGROUND: Cellular senescence and the senescence-associated secretory phenotype (SASP) may 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's disease. In this study, we investigated the roles of cellular senescence and Δ133p53, 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 p16INK4A and heterochromatin protein Hp1γ 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 Δ133p53 and induction of SASP. Lentiviral expression of ∆133p53 was performed to investigate its role in regulating radiation-induced cellular senescence and astrocyte-mediated neuroinflammation. RESULTS: Astrocytes expressing p16INK4A and Hp1γ were identified in all irradiated tissues, were increased in number in irradiated compared with untreated cancer patient tissues, and had higher labeling intensity in irradiated tissues compared with age-matched controls. Human astrocytes irradiated in vitro also experience induction of cellular senescence, have diminished Δ133p53, and adopt a neurotoxic phenotype as demonstrated by increased senescence-associated beta-galactosidase activity, p16INK4A, and interleukin (IL)-6. In human astrocytes, Δ133p53 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, ∆133p53, protects astrocytes from radiation-induced senescence, promotes DNA repair, and inhibits astrocyte-mediated neuroinflammation.
- 650 _2
- $a astrocyty $x metabolismus $x účinky záření $7 D001253
- 650 _2
- $a nádory mozku $x radioterapie $7 D001932
- 650 _2
- $a kultivované buňky $7 D002478
- 650 _2
- $a stárnutí buněk $x účinky záření $7 D016922
- 650 _2
- $a kraniální ozáření $x škodlivé účinky $7 D016371
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a protein - isoformy $x metabolismus $7 D020033
- 650 _2
- $a radiační poranění $x metabolismus $7 D011832
- 650 _2
- $a nádorový supresorový protein p53 $x metabolismus $7 D016159
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Extramural $7 D052061
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Beck, Jessica A $u Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 700 1_
- $a Horikawa, Izumi $u Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 700 1_
- $a Obiorah, Ifeyinwa E $u Department of Pathology, Georgetown University Medical Center, Washington, DC, USA.
- 700 1_
- $a Von Muhlinen, Natalia $u Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 700 1_
- $a Vojtesek, Borivoj $u Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
- 700 1_
- $a Lane, David P $u p53 Laboratory, Biomedical Sciences Institutes (A*STAR), Singapore.
- 700 1_
- $a Grunseich, Christopher $u Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
- 700 1_
- $a Chahine, Joeffrey J $u Department of Pathology, Georgetown University Medical Center, Washington, DC, USA.
- 700 1_
- $a Ames, Heather M $u Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA. Department of Pathology, University of Maryland, Baltimore, Maryland, USA.
- 700 1_
- $a Smart, Dee Dee $u Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 700 1_
- $a Harris, Brent T $u Department of Pathology, Georgetown University Medical Center, Washington, DC, USA. Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
- 700 1_
- $a Harris, Curtis C $u Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 773 0_
- $w MED00193498 $t Neuro-oncology $x 1523-5866 $g Roč. 21, č. 4 (2019), s. 474-485
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30615147 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20201125 $b ABA008
- 991 __
- $a 20201214124849 $b ABA008
- 999 __
- $a ok $b bmc $g 1595157 $s 1113514
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 21 $c 4 $d 474-485 $e 20190318 $i 1523-5866 $m Neuro-oncology $n Neuro Oncol $x MED00193498
- LZP __
- $a Pubmed-20201125