Loss of phosphoserine polar group asymmetry and inhibition of cholesterol transport in Jurkat cells treated with cholesterylphosphoserine

Journal of Lipid Research

Francesca Calderazzo¹  Federico Cusinato²  Walter Habeler²  Francesca Nardi²  Alessandro Bruni³ 

[1] Department of Oncological and Surgical Sciences, University of Padova, Via Gattamelata, 35128 Padova, Italy;Department of Pharmacology, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy;To whom correspondence should be addressed.;

关键词: progesterone;    sphingolipid-based domains;    caveolae;    phospholipid asymmetry;    annexin V;    cholesterol transport;   

DOI  :  

来源: DOAJ

【 摘 要 】

Cholesterylphosphoserine (CPHS) is a synthetic ester of cholesterol showing immunosuppressive activity. In the present study, we have used the T cell line Jurkat to investigate its mechanism of action. CPHS incorporates into cells reaching a molar ratio of 0.23 and 3.9 with the total phospholipid and cholesterol content, without inducing necrosis or apoptosis. CPHS incorporation elicits a dose-dependent binding of fluorescein isothiocyanate-labeled annexin V, suggesting that the steroid distributes in the external leaflet of plasma membrane exposing the phosphoserine group to the external cell environment and inserting the steroid ring into the phospholipid bilayer. In agreement with a preferential steroid association with sphingolipids, CPHS is included in a Triton X-100-insoluble complex when mixed with sphingomyelin and cholesterol. CPHS incorporation inhibits the esterification of low density lipoprotein (LDL)-derived cholesterol, producing a minor influence on the endogenous synthesis of cholesterol and on the acyl-CoA:cholesterol acyltransferase activity. In this effect, CPHS is as potent as progesterone (IC50 of 3.5 μm). It is concluded that the insertion of cholesterylphosphoserine (CPHS) in the Jurkat plasma membrane neutralizes the asymmetric distribution of the phosphoserine group and inhibits the movement of cholesterol to the endoplasmic reticulum. As CPHS is a negatively charged steroid, this last effect may be linked to the perturbation of sphingolipid/cholesterol-based microdomains, proposed to play a role in cholesterol trafficking.—Cusinato, F., W. Habeler, F. Calderazzo, F. Nardi, and A. Bruni. Loss of phosphoserine polar group asymmetry and inhibition of cholesterol transport in Jurkat cells treated with cholesterylphosphoserine.

【 授权许可】

Unknown