S1582 Start Domain Protein Stard4 Is Able to Bind Free Cholesterol and Increases Cholesterol Ester Formation and Microsomal Acat Activity

2008 ◽  
Vol 134 (4) ◽  
pp. A-776
Author(s):  
Daniel Rodriguez-Agudo ◽  
Shunlin Ren ◽  
Eric Wong ◽  
Dalila Marques ◽  
Kaye Redford ◽  
...  
Keyword(s):  
Cholesterol Ester ◽  
Free Cholesterol ◽  
Acat Activity ◽  
Ester Formation ◽  
Start Domain ◽  
Domain Protein

Studies on the rapid cholesterol-depleting and steroidogenic actions of luteinizing hormone in the rat ovary: effects of aminoglutethimide phosphate

1970 ◽  
Vol 48 (8) ◽  
pp. 881-884 ◽  
Author(s):  
Harold R. Behrman ◽  
David T. Armstrong ◽  
Roy O. Greep
Keyword(s):  
Luteinizing Hormone ◽  
Cholesterol Ester ◽  
Free Cholesterol ◽  
Tissue Concentration ◽  
Control Level ◽  
Side Chain ◽  
Tissue Levels ◽  
Chain Cleavage ◽  
Luteal Tissue ◽  
Rat Ovary

Superovulated, immature rats were administered luteinizing hormone (LH) and/or aminoglutethimide phosphate (AGP), an inhibitor of cholesterol side-chain cleavage, to ascertain whether the steroidogenic action could be separated from the cholesterol-depleting action of LH. The injection of AGP [Formula: see text] and [Formula: see text] before sacrifice significantly reduced tissue levels of progesterone and 20α-dihydroprogesterone to 25–30% of normal, and increased tissue levels of free cholesterol in the absence and presence of LH given [Formula: see text] or 4 h before sacrifice. Cholesterol ester concentration was increased twofold after [Formula: see text] AGP, whereas LH injection [Formula: see text] after AGP and 4 h before sacrifice reduced the tissue concentration to the control level but not as low as that observed when only LH was given 4 h before sacrifice (50% of control level). The cholesterol ester depletion induced by LH, even though steroidogenesis was inhibited, indicates that these may represent separate events in the action of LH on luteal tissue.

Role of renin-angiotensin system in activation of macrophages by modified lipoproteins

2013 ◽  
Vol 305 (9) ◽  
pp. H1309-H1320 ◽  
Author(s):  
Naimeh Rafatian ◽  
Ross W. Milne ◽  
Frans H. H. Leenen ◽  
Stewart C. Whitman
Keyword(s):  
Angiotensin Ii ◽  
Cholesterol Ester ◽  
Foam Cell ◽  
Cell Formation ◽  
Renin Angiotensin System ◽  
Foam Cell Formation ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Ester Formation ◽  
In Cells

Angiotensin II favors the development of atherosclerosis. Our goal was to determine if foam cell formation increases angiotensin II generation by the endogenous renin-angiotensin system (RAS) and if endogenously produced angiotensin II promotes lipid accumulation in macrophages. Differentiated THP-1 cells were treated with acetylated low-density lipoproteins (ac-LDL), native LDL (n-LDL), or no LDL. Expression of RAS genes was assessed and angiotensin I/II levels were quantified in media and cell lysate. Ac-LDL increased angiotensin I/II levels and the angiotensin II/I ratio in cells and media after foam cell formation. Renin mRNA or activity did not change, but renin blockade completely inhibited the increase in angiotensin II. Angiotensinogen mRNA but not protein level was increased. Angiotensin-converting enzyme (ACE) and cathepsin G mRNA and activities were enhanced by ac-LDL. Inhibition of renin, ACE, or the angiotensin II receptor 1 (AT1-receptor) largely abolished cholesteryl ester formation in cells exposed to ac-LDL and decreased scavenger receptor A (SR-A) and acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT-1) protein levels. Inhibition of renin or the AT1-receptor in cells treated with oxidized LDL also decreased SR-A and ACAT-1 protein and foam cell formation. ac-LDL also increased angiotensin II by human peripheral blood monocyte-derived macrophages, whereas blockade of renin decreased cholesterol ester formation in these macrophages. These findings indicate that, during foam cell formation, angiotensin II generation by the endogenous RAS is stimulated and that endogenously generated angiotensin II is crucial for cholesterol ester accumulation in macrophages exposed to modified LDL.

scholarly journals Intracellular cholesterol transporter StarD4 binds free cholesterol and increases cholesteryl ester formation

2008 ◽  
Vol 49 (7) ◽  
pp. 1409-1419 ◽  
Author(s):  
Daniel Rodriguez-Agudo ◽  
Shunlin Ren ◽  
Eric Wong ◽  
Dalila Marques ◽  
Kaye Redford ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Free Cholesterol ◽  
Ester Formation ◽  
Intracellular Cholesterol

Effect of phospholipase a upon brain cholesterol ester formation

Lipids ◽  
1974 ◽  
Vol 9 (6) ◽  
pp. 440-442 ◽  
Author(s):  
Robert B. Ramsey ◽  
A. N. Davison
Keyword(s):  
Cholesterol Ester ◽  
Phospholipase A ◽  
Brain Cholesterol ◽  
Ester Formation

scholarly journals p38 Mitogen-activated Protein Kinase (MAPK) Promotes Cholesterol Ester Accumulation in Macrophages through Inhibition of Macroautophagy

2012 ◽  
Vol 287 (15) ◽  
pp. 11761-11768 ◽  
Author(s):  
Shuang Mei ◽  
Haihua Gu ◽  
Adam Ward ◽  
Xuefeng Yang ◽  
Huailan Guo ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cholesterol Ester ◽  
Free Cholesterol ◽  
Ldl Cholesterol ◽  
Foam Cell ◽  
Cell Formation ◽  
Mitogen Activated Protein Kinase ◽  
Foam Cell Formation ◽  
Cholesterol Esters ◽  
Intracellular Accumulation

p38 MAPK has been strongly implicated in the development of atherosclerosis, but its role in cholesterol ester accumulation in macrophages and formation of foam cells, an early step in the development of atherosclerosis, has not been investigated. We addressed this issue and made some brand new observations. First, elevated intracellular cholesterol level induced by the exposure to LDL-activated p38 MAPK and activation of p38 MAPK with anisomycin increased the ratio of cholesterol esters over free cholesterol, whereas inhibition of p38 MAPK with SB203580 or siRNA reduced the LDL loading-induced intracellular accumulation of free cholesterol and cholesterol esters in macrophages. Second, exposure to LDL cholesterol inhibited autophagy in macrophages, and inhibition of autophagy with 3-methyladenine increased intracellular accumulation of cholesterol (free cholesterol and cholesterol esters), whereas activation of autophagy with rapamycin decreased intracellular accumulation of free cholesterol and cholesterol esters induced by the exposure to LDL cholesterol. Third, LDL cholesterol loading-induced inhibition of autophagy was prevented by blockade of p38 MAPK with SB203580 or siRNA. Neutral cholesterol ester hydrolase was co-localized with autophagosomes. Finally, LDL cholesterol loading and p38 activation suppressed expression of the key autophagy gene, ulk1, in macrophages. Together, our results provide brand new insight about cholesterol ester accumulation in macrophages and foam cell formation.

scholarly journals Cellular cholesterol ester accumulation induced by free cholesterol-rich lipid dispersions.

1976 ◽  
Vol 73 (10) ◽  
pp. 3680-3684 ◽  
Author(s):  
L. Y. Arbogast ◽  
G. H. Rothblat ◽  
M. H. Leslie ◽  
R. A. Cooper
Keyword(s):  
Cholesterol Ester ◽  
Free Cholesterol ◽  
Cellular Cholesterol

scholarly journals StarD10, a START Domain Protein Overexpressed in Breast Cancer, Functions as a Phospholipid Transfer Protein

2005 ◽  
Vol 280 (29) ◽  
pp. 27436-27442 ◽  
Author(s):  
Monilola A. Olayioye ◽  
Stefanie Vehring ◽  
Peter Müller ◽  
Andreas Herrmann ◽  
Jürgen Schiller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Start Domain ◽  
Domain Protein

scholarly journals Liver X receptor inhibition potentiates mitotane-induced adrenotoxicity in ACC

2020 ◽  
Vol 27 (6) ◽  
pp. 361-373
Author(s):  
Kate M Warde ◽  
Erik Schoenmakers ◽  
Eduardo Ribes Martinez ◽  
Yi Jan Lim ◽  
Maeve Leonard ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Cholesterol Ester ◽  
Free Cholesterol ◽  
Cholesterol Metabolism ◽  
Apoptotic Cell ◽  
Treatment Options ◽  
Liver X Receptor ◽  
Resistant Disease ◽  
Cholesterol Storage

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with a poor outcome largely due to limited treatment options. Here, we propose a novel therapeutic approach through modulating intracellular free cholesterol via the liver X receptor alpha (LXRα) in combination with current first-line pharmacotherapy, mitotane. H295R and MUC-1 ACC cell lines were pretreated with LXRα inhibitors in combination with mitotane. In H295R, mitotane (20, 40 and 50 µM) induced dose-dependent cell death; however, in MUC-1, this only occurred at a supratherapeutic concentration (200 µM). LXRα inhibition potentiated mitotane-induced cytotoxicity in both cell lines. This was confirmed through use of the CompuSyn model which showed moderate pharmacological synergism and was indicative of apoptotic cell death via an increase in annexinV and cleaved-caspase 3 expression. Inhibition of LXRα was confirmed through downregulation of cholesterol efflux pumps ABCA1 and ABCG1; however, combination treatment with mitotane attenuated this effect. Intracellular free-cholesterol levels were associated with increased cytotoxicity in H295R (r2 = 0.5210) and MUC-1 (r2 = 0.9299) cells. While both cell lines exhibited similar levels of free cholesterol at baseline, H295R were cholesterol ester rich, whereas MUC-1 were cholesterol ester poor. We highlight the importance of LXRα mediated cholesterol metabolism in the management of ACC, drawing attention to its role in the therapeutics of mitotane sensitive tumours. We also demonstrate significant differences in cholesterol storage between mitotane sensitive and resistant disease.

Sign in / Sign up

Export Citation Format

Share Document