Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
I GrechowaBernhard Dorweiler

Abstract

Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT-PCR, immunocytochemistry, and Western blot. Genetic silencing of CHOP was achieved by small interfering RNA. Elastase induces autophagic-apoptotic forms of endothelial cell death in a time- and dose-dependent manner, in conjunction with a significant increase in phosphorylation/expression of the canonical UPR-activation markers PERK and CHOP. By using CHOP knockdown, we identified CHOP as a key mediator of elastase-induced endothelial cell death. Immunohistochemical analysis of human rupture-prone plaque specimens confirmed the presence of elastase and colocalization with apoptosis. We have demonstrated for th...Continue Reading

References

Jun 1, 1990·Journal of the American College of Cardiology·J L DinermanA Davidson
Sep 23, 2000·Nature·A J Lusis
Dec 4, 2002·Circulation·Takahiko NarukoAnton E Becker
May 29, 2003·Circulation·Clare M DolleryPeter Libby
Dec 4, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Ken A Lindstedt, Petri T Kovanen
Apr 2, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Arturo Garcia-TouchardRobert S Schwartz
May 14, 2005·American Journal of Respiratory Cell and Molecular Biology·Tomoko SuzukiGregory P Downey
May 17, 2005·Journal of the American College of Cardiology·Benjamin D HorneUNKNOWN Intermountain Heart Collaborative Study Group
Jun 15, 2005·Annual Review of Biochemistry·Martin Schröder, Randal J Kaufman
Dec 27, 2005·Cardiovascular Research·Clare M Dollery, Peter Libby
Jan 3, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Jeanna JacobiBatya Kristal
Mar 18, 2006·Thrombosis and Haemostasis·Bernhard DorweilerChristian-Friedrich Vahl
Sep 6, 2006·Circulation·Andrew J LegerAthan Kuliopulos
Sep 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jasimuddin AhamedWolfram Ruf
Apr 5, 2007·Nature Protocols·Carlo Riccardi, Ildo Nicoletti
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Dec 7, 2007·British Journal of Pharmacology·R Ramachandran, M D Hollenberg
Feb 22, 2008·The International Journal of Biochemistry & Cell Biology·Peter A Henriksen, Jean-Michel Sallenave
Oct 1, 2008·Nature Reviews. Immunology·Christian WeberPeter Libby
Mar 25, 2009·American Journal of Respiratory Cell and Molecular Biology·Tomoko SuzukiGregory P Downey
Oct 16, 2009·The New England Journal of Medicine·Richard S HotchkissPaul E Swanson
Apr 9, 2010·Nature Medicine·Gökhan S Hotamisligil
May 18, 2010·The American Journal of Pathology·Pierre RotziusEinar E Eriksson
Jul 3, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Mihaela G IonitaDominique P V de Kleijn
Oct 30, 2010·Circulation Research·Tetsuo MinaminoMasafumi Kitakaze
Nov 30, 2010·Cell Death and Differentiation·C MullerC Vindis
Mar 3, 2011·Nature Cell Biology·Ira Tabas, David Ron
May 3, 2011·Cell·Kathryn J Moore, Ira Tabas
May 18, 2011·The Journal of Biological Chemistry·Rithwik RamachandranMorley D Hollenberg
Oct 15, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Cameron S McAlpineGeoff H Werstuck
Nov 19, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Christopher M Scull, Ira Tabas

❮ Previous
Next ❯

Citations

Jan 4, 2020·Journal of Thrombosis and Thrombolysis·Richard C BeckerSakthivel Sadayappan
Sep 19, 2019·Experimental Animals·Yiwei FengAnzhou Tang
Feb 15, 2020·International Journal of Molecular Sciences·Katharine M LodgeAlison M Condliffe
Nov 7, 2019·Oxidative Medicine and Cellular Longevity·Xinnong ChenJunping Zhang
Jan 31, 2020·Frontiers in Immunology·Johannes WestmanPedro Elias Marques
May 18, 2020·Journal of Thrombosis and Thrombolysis·Richard C Becker
Sep 12, 2020·American Journal of Respiratory Cell and Molecular Biology·Sanaz DastghaibAmir A Zeki
Jan 16, 2021·International Journal of Molecular Sciences·Margarita A SazonovaIgor A Sobenin
Apr 2, 2021·International Journal of Cardiology·Ampadu O JacksonShiyin Long
Apr 3, 2021·Frontiers in Cellular and Infection Microbiology·Hisanori Domon, Yutaka Terao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Related Papers

European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery
B DorweilerS Horke
Arteriosclerosis, Thrombosis, and Vascular Biology
Christopher M Scull, Ira Tabas
© 2022 Meta ULC. All rights reserved