Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life

The Journal of Biological Chemistry
Gang TianNick Platt

Abstract

The class A scavenger receptor (SR-A) is a multifunctional trimeric membrane glycoprotein involved in atherogenesis. The mature receptor can mediate the binding and internalization of a number of specific ligands, including modified low-density lipoprotein. We have investigated the effects of inhibiting N-glycan processing on SR-A expression, distribution, and activity in the murine macrophage cell line RAW264.7. We have found that SR-A normally interacts with calnexin in the endoplasmic reticulum and in its mature form carries complex N-glycans. The imino sugar, N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of the N-glycan processing enzymes alpha-glucosidases I and II. Following NB-DNJ treatment SR-A became Endo H-sensitive, consistent with inhibition of N-glycan processing. A dose-dependent increase in cell surface expression of SR-A was observed in response to NB-DNJ treatment. The receptor on inhibitor-treated cells was still functional because the increased surface expression resulted in a proportional enhancement in the endocytosis of the ligand, acetylated low-density lipoprotein. The expression of SR-A on NB-DNJ cultured cells was further enhanced by co-treatment with interferon-gamma. Quantitative reverse transcrip...Continue Reading

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Citations

May 12, 2010·Journal of Inherited Metabolic Disease·Danielle te VruchteDaniel John Sillence
Sep 9, 2005·Current Opinion in Lipidology·Theo J C van BerkelMiranda van Eck
Jan 11, 2011·American Journal of Respiratory Cell and Molecular Biology·Lynnelle A PittetJoseph P Mizgerd
Dec 15, 2006·The Journal of Biological Chemistry·Yi-Ling LinJohn P Williams
Jan 24, 2007·The Journal of Biological Chemistry·Hitomi SanoYoshio Kuroki
Jun 4, 2019·Biological & Pharmaceutical Bulletin·Kiyomi NigorikawaKaoru Hazeki
Aug 22, 2006·Bioorganic & Medicinal Chemistry·Liang YuNaoki Asano

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