Functional relevance of Golgi- and plasma membrane-localized endothelial NO synthase in reconstituted endothelial cells

Arteriosclerosis, Thrombosis, and Vascular Biology
Qian ZhangDavid Fulton

Abstract

We have previously shown in COS-7 cells that targeting of endothelial NO synthase (eNOS) to the Golgi or plasma membrane (PM) regulates the mechanism and degree of eNOS activation. However, little is known about the functional significance of eNOS targeting in endothelial cells (ECs). The goal of the current study was to isolate these 2 pools of enzyme in ECs and determine their functional significance in response to agonist stimulation and manipulation of membrane cholesterol levels. Using an RNA interference strategy, we generated stable populations of ECs that had >90% inhibition of eNOS expression and lacked the ability to produce NO. Reconstitution of these eNOS "knockdown" ECs with Golgi- and PM-targeted eNOS restored the ability of ECs to produce NO. Calcium-dependent agonists were the more efficient stimulus for the PM-restricted eNOS in ECs. In contrast, Golgi eNOS was less responsive to both calcium- and Akt-dependent agonists. eNOS restricted to the PM was more sensitive to manipulation of membrane cholesterol levels and was significantly attenuated by modified low-density lipoprotein. Within ECs, the PM is the most efficient location to produce NO but is more vulnerable to cholesterol levels and modified low-density...Continue Reading

References

Mar 15, 1996·The Journal of Biological Chemistry·P W ShaulT Michel
Mar 21, 1998·The Journal of Clinical Investigation·R D RudicW C Sessa
Aug 8, 1998·The Journal of Biological Chemistry·T Furuchi, R G Anderson
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·G SowaW C Sessa
Aug 28, 2003·Nature Cell Biology·Carol A SledzBryan R G Williams
May 27, 2005·American Journal of Physiology. Cell Physiology·Davin JagnandanDavid Fulton

❮ Previous
Next ❯

Citations

May 1, 2007·Cardiovascular Research·David M Dudzinski, Thomas Michel
Jul 16, 2011·The Journal of Biological Chemistry·Fabiola A SánchezWalter N Durán
Apr 1, 2009·Antioxidants & Redox Signaling·David J R Fulton
Dec 19, 2012·Antioxidants & Redox Signaling·Xutong SunStephen M Black
Nov 20, 2012·Antioxidants & Redox Signaling·Antonio Martínez-RuizJuan M Serrador
May 14, 2010·Cardiovascular Research·Walter N DuránFabiola A Sánchez
Sep 21, 2010·Cardiovascular Research·Christopher B PattilloChristopher G Kevil
Jan 9, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yukio HiroiJames K Liao
Oct 27, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jin QianDavid J R Fulton
Aug 19, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Fabiola A SánchezWalter N Durán
Jun 17, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Qian ZhangDavid J R Fulton
Jul 31, 2012·American Journal of Respiratory Cell and Molecular Biology·Cristina M AlviraDavid N Cornfield
Nov 27, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Marcus BaumannJo G R De Mey
Aug 20, 2015·Science Signaling·Mauro SiragusaWilliam C Sessa
Apr 20, 2014·BioMed Research International·Jacques Noireaud, Ramaroson Andriantsitohaina
May 18, 2016·Pflügers Archiv : European journal of physiology·Mauro Siragusa, Ingrid Fleming
Sep 8, 2007·Vascular Pharmacology·Chunying LiRichard C Venema
Dec 16, 2016·American Journal of Physiology. Cell Physiology·Kedar GhimireJeffrey S Isenberg
May 11, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sharang GhavampourSüleyman Ergün
Apr 22, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Zheng-Gen Jin
Oct 31, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Somshuvra MukhopadhyayPravin B Sehgal
Dec 17, 2014·Angiogenesis·Mani Krishna PriyaSuvro Chatterjee
Mar 29, 2014·Pharmacological Reviews·Marie BillaudBrant E Isakson
Feb 1, 2017·Cellular and Molecular Bioengineering·Allison M AndrewsKenneth A Barbee
Dec 14, 2006·The Journal of Biological Chemistry·Davin JagnandanDavid J R Fulton
Mar 11, 2020·Nature Chemical Biology·Maulik S JaniYamuna Krishnan
Jun 25, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Shawn ElmsDavid J R Fulton
May 28, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Sheila FlavahanNicholas A Flavahan
Mar 23, 2018·Molecular Biology of the Cell·Zhenlong ChenRichard D Minshall
Jan 11, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Snježana RadulovićSaša Frank
Nov 4, 2020·Nature Nanotechnology·Anand SaminathanYamuna Krishnan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.