Lipoprotein-associated estrogens

Tikkanen, Matti J.; Vihma, Veera; Jauhiainen, Matti; Höckerstedt, Anna; Helisten, Hannamaarit; Kaamanen, Maija

doi:10.1016/s0008-6363(02)00535-7

Cited by 48 publications

(37 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several compounds, including estrogens, have been shown to reduce oxidative stress on neurons [5,6,13,15,17]. In addition to binding to ERs in the cellular membrane, cytoplasm and nucleus [48], estrogens may also interact with lipid-transport proteins [49]. Because of their lipophilicity, they also concentrate in lipid-rich regions of cells such as cellular membranes and affecting and, thereby, have been shown to affect membrane fluidity [50].…”

Section: Discussionmentioning

confidence: 99%

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

et al. 2008

View full text Add to dashboard Cite

Antioxidant action is an important component of the complex neuroprotective action of estrogens. Combining theoretical prediction and subsequent experimental confirmation by chemical and in vitro paradigms, this study focused on the mechanistic aspects of hydroxyl-radical scavenging by 17β-butoxy-1,3,5(10)-estratrien-3-ol, a synthetic derivative of 17β-estradiol with increased potency to inhibit lipid peroxidation and reduced affinity to estrogen-receptors compared to the endogenous hormone. In the process that acts as a "chemical shield," the phenolic A-ring turns into 10β-hydroxy-17β-butoxy-1,3,5(10)-estratrien-3-one, a non-aromatic para-quinol, upon capturing hydroxyl-radicals, which results in the complete loss of estrogen-receptor affinity and antioxidant activity. However, the parent compound is apparently recovered in brain tissue from this para-quinol via enzyme-catalyzed NAD(P)H-dependent reductive aromatization without causing oxidative stress. Taken together, our report argues for a previously unrecognized antioxidant cycle for synthetic estrogen-derived compounds.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Other sterols are present in HDL at much lower levels as exemplifi ed by minor amounts of oxysterols (27-hydroxycholesterol, 24-hydroxycholesterol, cholesterol-5,6-␤ -epoxide, and 7-ketocholesterol) ( 36 ); estrogens (largely present as esters) ( 37 ); and phytosterols.…”

Section: Steroidsmentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

310

247

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org For many years, HDL lipids were predominantly characterized in terms of the content of their major classes, notably phospholipids, unesterifi ed (free) sterols (predominantly cholesterol), cholesteryl esters, and triglycerides. Cholesterol is the most characteristic component of the HDL lipidome as, in the form of HDL-cholesterol, it represents a major independent negative risk factor for cardiovascular disease (see other reviews in this Thematic Series). It is not cholesterol, however, but phospholipids that quantitatively predominate in the HDL lipidome, accounting, together with sphingomyelin (SM), for 40-60 wt% of total lipid, with lesser proportions of cholesteryl esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Structurally, individual HDL lipid classes fulfi ll distinct functions; phospholipids constitute the surface lipid monolayer of HDL, whereas cholesteryl esters and triglycerides form the hydrophobic lipid core. Unesterifi ed sterols are predominantly located to the surface monolayer, partially penetrating the core.Recent technological advances in mass spectrometry (MS) have enabled application of this powerful technique to provide a detailed identifi cation and quantifi cation of individual molecular species of lipids in the framework of the fi eld known as lipidomics. Application of this approach to plasma lipoproteins has revealed complex profi les consisting of hundreds of molecular lipid species that have been quantifi ed in major lipoprotein classes, including HDL (reviewed in Refs. 1-3 High density lipoproteins (HDL) are small, dense, protein-rich particles compared with other plasma lipoprotein classes. Despite the elevated abundance of multiple structural and functional proteins in HDL particles (see other reviews in this Thematic Series), roughly half of total HDL mass is accounted for by lipid components.

show abstract

“…2 ) To explore a possible lipid transfer mechanism mediated by CETP upon penetration. 3 ) ␤ -Estradiol (E 2 ) molecules are transported in plasma lipoproteins mostly as fatty acyl derivatives, HDL, in particular, is reported to be a good carrier for E 2 fatty acyl ester ( 6, 7 ) and the HDL/E 2 fatty acyl ester complex has an enhanced atheroprotective role, at least in vitro, particularly among women ( 6,8,9 ). Furthermore, experimental fi ndings indicate that esterifi ed estradiol molecules are transferred from HDL to LDL particles via a CETP-mediated process, the details of which are unknown ( 10 ).…”

Section: Atomistic MD Simulation Parameters and Force Fi Eldmentioning

confidence: 99%

Atomistic MD simulation reveals the mechanism by which CETP penetrates into HDL enabling lipid transfer from HDL to CETP

Cilpa-Karhu

Jauhiainen

Riekkola

2015

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org the atheroprotective functions of HDL ( 1 ) have been driving forces for research on HDL as a potential therapeutic target ( 2 ). Several therapies aimed at increasing HDL-C levels have been tested. Among them is the inhibition of cholesterol ester transfer protein (CETP) ( 2, 3 ), a plasma neutral lipid transfer protein that mediates exchange/ transfer of neutral lipids between HDL and apoB-100-containing lipoproteins and is involved in the reverse cholesterol transport process. Despite an increase in the level of HDL-C, there was no decrease in cardiovascular risk. This outcome shows that the direct relationship between increase in HDL-C and decrease in the risk for cardiovascular disease is not clear and some of the characteristics of HDL and/or CETP are not yet known, preventing full comprehension of the mechanism by which CETP interacts with HDL to facilitate lipid transfer in the circulation. Our objective was then to clarify the process by which CETP binds and interacts with HDL.Atomistic molecular dynamics (MD) and coarse graining dynamics studies ( 4 ) have previously been applied to clarify the lipid transfer from HDL mediated by CETP. The HDL model was a lipid-mimicking droplet of HDL containing phospholipids (POPC) and cholesteryl ester, lacking the HDL main protein, apoA-I. While these previous computational studies considered a match to match curvature CETP-HDL, a recent experimental study relying on advanced electron microscopy (EM) technique and 3D reconstruction demonstrated that CETP and HDL form a binary complex by partial penetration of CETP into the lipid-apolipoprotein monolayer surface of HDL, with The well-recognized associations between the plasma level of HDL-cholesterol (HDL-C), HDL metabolism, and

show abstract

Lipoprotein-associated estrogens

Cited by 48 publications

References 41 publications

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

Unraveling the complexities of the HDL lipidome

Atomistic MD simulation reveals the mechanism by which CETP penetrates into HDL enabling lipid transfer from HDL to CETP

Contact Info

Product

Resources

About