Sac1 Phosphoinositide Phosphatase Regulates Foam Cell Formation by Modulating SR-A Expression in Macrophages.

Sac1 Phosphoinositide Phosphatase Regulates Foam Cell Formation by Modulating SR-A Expression in Macrophages.
Biol Pharm Bull. 2019;42(6):923-928
Authors: Nigorikawa K, Matsumura T, Sakamoto H, Morioka S, Kofuji S, Takasuga S, Hazeki K
Abstract
Macrophages endocytose modified low-density lipoproteins (LDL) vigorously via scavenger receptor A (SR-A) to become foam cells. In the present study, we found that Sac1, a member of the Sac family of phosphoinositide phosphatases, increases the protein level of SR-A and upregulates foam cell formation. Mouse macrophages (RAW264.7) were transfected with short hairpin RNAs (shRNAs) against Sac1. Sac1 knockdown decreased cell surface SR-A levels and impaired acetylated LDL-induced foam cell formation. Transfection of Sac1-knockdown cells with shRNA-resistant flag-Sac1 effectively rescued the expression of SR-A. Glycosylation of SR-A was largely attenuated by Sac1 knockdown, but neither mRNA expression nor protein degradation of SR-A were affected. These results suggest that Sac1 maintains SR-A protein levels by modulating SR-A glycosylation.
PMID: 31155588 [PubMed - in process]

Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Nigorikawa K, Matsumura T, Sakamoto H, Morioka S, Kofuji S, Takasuga S, Hazeki K Tags: Biol Pharm Bull Source Type: research