This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeng, L. Articles by Xu, Q. Search for Related Content PubMed PubMed Citation Articles by Zeng, L. Articles by Xu, Q. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL Related Collections Related Article

(Circulation Research. 2008;103:10.)
© 2008 American Heart Association, Inc.

Editorials

eNOS–ER Complex Goes to Telomerase

Lingfang Zeng, Qingbo Xu

From the Cardiovascular Division, King’s College London BHF Centre, London, UK.

Correspondence to Professor Qingbo Xu, Cardiovascular Division, King’s College London BHF Centre, London SE5 9NU, UK. E-mail qingbo.xu@kcl.ac.uk

See related article, pages 34–42

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Nitric oxide (NO) plays an important role not only in physiological conditions,¹ such as vasodilation, inhibition of platelet aggregation, and regulation of gene transcription,² but also in atherosclerosis development. NO is synthesized from L-arginine by a family of 3 NO synthases (NOS): neuronal (nNOS),³ inducible (iNOS),⁴ and endothelial (eNOS).⁵ eNOS possesses an N-terminal oxygenase domain containing single heme and tetrahydrobioperin (BH-4)-binding sites, a C-terminal reductase domain containing single binding sites for flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and NADPH, and a central calmodulin (CaM) binding site.⁶ eNOS is specifically and constitutively expressed in endothelial cells normally localized in caveolae, endoplamic reticulum, and nuclear envelop.⁷ In caveolae, eNOS associates with growth factor or hormone receptors. On ligand-receptor binding, the receptor-associated eNOS will be phosphorylated, homodimerized, and coupled with CaM together with cofactors BH4, heme, FAD, FMN, and NADPH to form a complex. The complex will be translocated to endoplamic reticulum via caveolin and oxidize L-arginine to release NO. However, under oxidative stress conditions, caused by atherosclerotic risk factors—such as cholesterol overloading, oxidized LDL, smoking, diabetes mellitus, etc—eNOS will be uncoupled to produce superoxide.^7,8 Thus, eNOS can produce both NO and superoxide, exerting atheroprotective and proatherogenic effects, by which it modulates gene transcription. Recently, several reports have shown that activated eNOS can translocate into nucleus where it regulates gene transcription.^9–12 However, the underlying mechanism remains unclear.

	ER and eNOS Form a Complex That Enhances Telomerase Activation

 
Estrogen is an important atheroprotective molecule, possessing multiple biological effects on vasculature. There are two estrogen receptor (ER) isoforms, ER alpha (ER) and ER . . . [Full Text of this Article]

Related Article:

Estrogen Receptor- and Endothelial Nitric Oxide Synthase Nuclear Complex Regulates Transcription of Human Telomerase

Annalisa Grasselli, Simona Nanni, Claudia Colussi, Aurora Aiello, Valentina Benvenuti, Gianluca Ragone, Fabiola Moretti, Ada Sacchi, Silvia Bacchetti, Carlo Gaetano, Maurizio C. Capogrossi, Alfredo Pontecorvi, and Antonella Farsetti
Circ. Res. 2008 103: 34-42. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				A. Farsetti, A. Grasselli, S. Bacchetti, C. Gaetano, and M. C. Capogrossi The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling J Appl Physiol, January 1, 2009; 106(1): 333 - 337. [Abstract] [Full Text] [PDF]