Telomerase deficiency delays renal recovery in mice after ischemia-reperfusion injury by impairing autophagy

Kidney International
Huifang ChengRaymond C Harris

Abstract

The aged population suffers increased morbidity and higher mortality in response to episodes of acute kidney injury (AKI). Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length. To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice or mice with either TerC or TerT deletion. Injury induced similar renal impairment at day 1 in each genotype, as assessed by azotemia, proteinuria, acute tubular injury score, and apoptotic tubular epithelial cell index. However, either TerC or TerT knockout significantly delayed recovery compared with wild-type mice. Electron microscopy showed increased autophagosome formation in renal tubular epithelial cells in wild-type mice but a significant delay of their development in TerC and TerT knockout mice. There were also impeded increases in the expression of the autophagosome marker LC3 II, prolonged accumulation of the autophagosome protein P62, an increase of the cell cycle regulator p16, and greater activation of the mammalian target of rapamycin (mTOR) pathway. The mTORC1 inhibitor, rapamycin, partially restored the ischemia/reperfus...Continue Reading

References

Jan 1, 1979·Annual Review of Medicine·C L Hall, J Hardwicke
May 12, 2000·The Journal of Biological Chemistry·A M Cuervo, J F Dice
Jul 11, 2001·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·A DonatiE Bergamini
Jul 27, 2001·The Journal of Surgical Research·K K MeldrumA H Harken
Sep 24, 2005·Journal of the American Society of Nephrology : JASN·Glenn M ChertowDavid W Bates
Jan 4, 2007·The Journal of Pathology·J E Martin, M T Sheaff
Aug 2, 2007·Nature Reviews. Molecular Cell Biology·Judith Campisi, Fabrizio d'Adda di Fagagna
Sep 15, 2007·The Journal of Clinical Investigation·Huiling WuSteven J Chadban
Feb 2, 2008·Blood·Rodrigo T Calado, Neal S Young
Feb 9, 2008·Histochemistry and Cell Biology·Tino KurzUlf T Brunk
May 31, 2008·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Roland SchmittChirag R Parikh
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Mar 5, 2009·The Journal of Biological Chemistry·Ian G GanleyXuejun Jiang
Apr 8, 2009·The Journal of Clinical Investigation·Craig BrooksZheng Dong
Sep 22, 2009·Clinics in Geriatric Medicine·Khaled Abdel-Kader, Paul M Palevsky
Oct 31, 2009·Journal of the American Society of Nephrology : JASN·Wilfred Lieberthal, Jerrold S Levine
Nov 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stefan SchoeftnerMaria A Blasco
Dec 5, 2009·Journal of the American Society of Nephrology : JASN·Jens H WesthoffAnette Melk
Dec 17, 2009·The New England Journal of Medicine·Rodrigo T Calado, Neal S Young
Feb 4, 2010·Nature Reviews. Nephrology·Alexandra ChronopoulosClaudio Ronco
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Y Jeffrey ChiangRichard J Hodes
Jan 7, 2011·Journal of the American Society of Nephrology : JASN·Sharon AndersonKevin P High
Jan 7, 2011·Journal of the American Society of Nephrology : JASN·Lauren P Wills, Rick G Schnellmann
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Apr 16, 2011·Journal of the American Society of Nephrology : JASN·Tomonori KimuraYoshitaka Isaka
Sep 3, 2011·Cell·David C RubinszteinGuido Kroemer
Oct 1, 2011·American Journal of Physiology. Renal Physiology·David H LeeMatthew Plotkin
Nov 3, 2011·The Journal of Clinical Investigation·Joseph V Bonventre, Li Yang
Mar 8, 2012·Experimental Lung Research·Amber L DegryseWilliam E Lawson
Apr 13, 2012·American Journal of Physiology. Renal Physiology·Wilfred Lieberthal, Jerrold S Levine
Jun 14, 2012·Autophagy·Tobias B HuberZheng Dong
Aug 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Olga V LeontievaMikhail V Blagosklonny
Aug 3, 2012·Kidney International·Man JiangZheng Dong
Oct 23, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jun ArayaKazuyoshi Kuwano
Dec 12, 2012·Journal of the American Society of Nephrology : JASN·Raymond K HsuChi-yuan Hsu

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Citations

Aug 19, 2015·Mechanisms of Ageing and Development·Carolin SchildhornAnette Melk
Dec 25, 2015·Journal of the American Society of Nephrology : JASN·Mingjun ShiMing Chang Hu
Aug 23, 2016·Biochemical and Biophysical Research Communications·Muhammad AliHan-Woong Lee
Apr 28, 2018·Cell Transplantation·Lucia AndradeIrene L Noronha
Feb 26, 2019·Kidney Research and Clinical Practice·Junyong LeeMyung-Gyu Kim
Apr 21, 2017·American Journal of Physiology. Renal Physiology·Yang ZhouJunwei Yang
Jan 10, 2020·Journal of Cellular and Molecular Medicine·Bingru ZhouPing Zou
May 18, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xinyuan LiJie Li
Jun 9, 2020·Basic Research in Cardiology·William E HughesDavid D Gutterman
Aug 31, 2020·Hypertension·Yongxin Li, Lilach O Lerman
Mar 30, 2018·International Urology and Nephrology·Ming TangKe-Qin Zhang
Feb 2, 2017·Journal of the American Society of Nephrology : JASN·Eoin D O'SullivanDavid A Ferenbach
Aug 30, 2017·Frontiers in Pharmacology·Jing ChenXiaoqiang Ding
Feb 21, 2018·PloS One·Jae-Il RohHan-Woong Lee
Aug 14, 2018·Nucleic Acids Research·Maria RubtsovaOlga Dontsova
Jun 20, 2019·Frontiers in Genetics·Marisa Cañadas-GarreAlexander Peter Maxwell
Jul 25, 2020·Nature Reviews. Nephrology·Chengyuan TangZheng Dong
Nov 25, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·William E HughesDavid D Gutterman
Jan 9, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yao WangXingjie Ma
Dec 29, 2020·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Su Woong JungSang-Ho Lee
Nov 11, 2020·Cells·Yohan SantinAngelo Parini
Sep 4, 2020·Journal of Cellular and Molecular Medicine·Yu ZhongKan-Fu Peng
Jul 22, 2017·Kidney International·Roland Schmitt, Anette Melk
Oct 4, 2020·Experimental and Molecular Pathology·Kee Hwan YooEun Soo Bae

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Methods Mentioned

BETA
environmental stress
light
electron microscopy
ELISA
Assay

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