Ataxia telangiectasia mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence.

The Journal of Biological Chemistry
Hong ZhanRyozo Nagai

Abstract

Oxidative stress regulates dysfunction and senescence of vascular endothelial cells. The DNA damage response and its main signaling pathway involving ataxia telangiectasia mutated (ATM) have been implicated in playing a central role in mediating the actions of oxidative stress; however, the role of the ATM signaling pathway in vascular pathogenesis has largely remained unclear. Here, we identify ATM to regulate oxidative stress-induced endothelial cell dysfunction and premature senescence. Oxidative stress induced senescence in endothelial cells through activation/phosphorylation of ATM by way of an Akt/p53/p21-mediated pathway. These actions were abrogated in cells in which ATM was knocked down by RNA interference or inhibited by specific inhibitory compounds. Furthermore, the in vivo significance of this regulatory pathway was confirmed using ATM knock-out mice in which induction of senescent endothelial cells in the aorta in a diabetic mouse model of endothelial dysfunction and senescence was attenuated in contrast to pathological changes seen in wild-type mice. Collectively, our results show that ATM through an ATM/Akt/p53/p21-dependent signaling pathway mediates an instructive role in oxidative stress-induced endothelial d...Continue Reading

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Nov 23, 2000·Nature·T Finkel, N J Holbrook
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Mar 4, 2003·Nature Reviews. Cancer·Yosef Shiloh
Mar 5, 2003·Cellular and Molecular Life Sciences : CMLS·M ZafarullahM Ahmad
Nov 18, 2004·The Journal of Biological Chemistry·Juan Guinea ViniegraRicardo Sánchez-Prieto
Dec 22, 2004·Mechanisms of Ageing and Development·T von ZglinickiS P Jackson
Apr 15, 2005·Nature·Vassilis G GorgoulisThanos D Halazonetis
Apr 20, 2006·Nature Structural & Molecular Biology·Aude DupréJean Gautier
Jul 22, 2006·The EMBO Journal·Sergei V KozlovMartin F Lavin
Jan 6, 2007·Circulation Research·Tohru Minamino, Issei Komuro
Jun 17, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Hidetaka OtaYasuyoshi Ouchi
Sep 25, 2008·Nature Reviews. Molecular Cell Biology·Martin F Lavin
Nov 5, 2008·Molecular and Cellular Biology·Zuzana BencokovaEster M Hammond

❮ Previous
Next ❯

Citations

Jul 28, 2013·AJNR. American Journal of Neuroradiology·D D M LinT O Crawford
Dec 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Girija DasmahapatraSteven Grant
Jul 17, 2012·Nature Medicine·Yuji OkunoYoshiaki Kubota
Mar 5, 2015·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Raj BhayadiaMeike Hömme
Nov 15, 2011·Trends in Biochemical Sciences·Scott Ditch, Tanya T Paull
May 18, 2012·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Hiroshi ShigetomiHiroshi Kobayashi
Dec 18, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·Takafumi IshidaYasuki Kihara
Mar 1, 2012·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Ryan R Gordon, Peter S Nelson
Mar 19, 2014·Redox Biology·H Susana MarinhoFernando Antunes
Jun 15, 2011·DNA Repair·Michaela SemlitschErnst Malle
Jan 26, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Maqsood A SiddiquiSalman A Alrokayan
May 9, 2015·PloS One·José C M MombachCristhian A Bugs
Jul 9, 2016·Radiation Research·Yingying WangDaohong Zhou
Dec 15, 2017·Frontiers in Oncology·Erika S Dahl, Katherine M Aird
Jul 21, 2017·Journal of the American Heart Association·Lixin JiaJie Du
Dec 29, 2012·Journal of Veterinary Science·Min-A SeolSung-Kee Jo
Nov 7, 2013·G3 : Genes - Genomes - Genetics·Nadia Graciele KrohnGustavo Henrique Goldman
Aug 29, 2012·The Journal of Pharmacology and Experimental Therapeutics·Rachel W GoeheDavid A Gewirtz
May 5, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maëva GuillonneauIsabelle Corre
Dec 30, 2016·Chinese Medical Sciences Journal = Chung-kuo I Hsüeh K'o Hsüeh Tsa Chih·Guo-Wen LiKai Qing
Jan 25, 2019·Stem Cells International·L L AlekseenkoN N Nikolsky
Oct 23, 2014·The Journal of Biological Chemistry·Ryan T Y WuWen-Hsing Cheng
Apr 2, 2021·International Journal of Cardiology·Ampadu O JacksonShiyin Long
May 8, 2021·Frontiers in Neuroscience·Sara Rojas-VázquezIsabel Fariñas
Feb 17, 2011·Journal of Proteome Research·Amrita K CheemaAnatoly Dritschilo

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.