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

Biol Pharm Bull. 2019;42(6):923-928. doi: 10.1248/bpb.b18-00907.

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.

Keywords: Sac1; foam cell formation; lipid droplet; macrophage; phosphoinositide phosphatase; scavenger receptor A (SR-A).

MeSH terms

  • Animals
  • Foam Cells / metabolism*
  • Lipoproteins, LDL / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Phosphoinositide Phosphatases / genetics
  • Phosphoinositide Phosphatases / metabolism*
  • RAW 264.7 Cells
  • RNA, Messenger
  • RNA, Small Interfering
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism*

Substances

  • Lipoproteins, LDL
  • Membrane Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Sac1 protein, mammalian
  • Scavenger Receptors, Class A
  • Phosphoinositide Phosphatases