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


Journal

Biological & pharmaceutical bulletin
ISSN: 1347-5215
Titre abrégé: Biol Pharm Bull
Pays: Japan
ID NLM: 9311984

Informations de publication

Date de publication:
2019
Historique:
entrez: 4 6 2019
pubmed: 4 6 2019
medline: 26 11 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31155588
doi: 10.1248/bpb.b18-00907
doi:

Substances chimiques

Lipoproteins, LDL 0
Membrane Proteins 0
RNA, Messenger 0
RNA, Small Interfering 0
Sac1 protein, mammalian 0
Scavenger Receptors, Class A 0
Phosphoinositide Phosphatases EC 3.1.3.36

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

923-928

Auteurs

Kiyomi Nigorikawa (K)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

Takuma Matsumura (T)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

Hiromi Sakamoto (H)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

Shin Morioka (S)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

Satoshi Kofuji (S)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

Shunsuke Takasuga (S)

Department of Pathology and Immunology, Akita University School of Medicine.

Kaoru Hazeki (K)

Graduate School of Biomedical & Health Sciences, Hiroshima University.

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Classifications MeSH