1. Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation
- Author
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Qin, Yuanyuan, Ting, Flora, Kim, Mee J, Strelnikov, Jacob, Harmon, Joseph, Gao, Feng, Dose, Andrea, Teng, Ba-Bie, Alipour, Mohsen Amir, Yao, Zemin, Crooke, Rosanne, Krauss, Ronald M, and Medina, Marisa W
- Subjects
Nutrition ,Liver Disease ,Digestive Diseases ,Atherosclerosis ,Underpinning research ,1.1 Normal biological development and functioning ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Cholesterol ,Diet ,High-Fat ,Down-Regulation ,Female ,Hep G2 Cells ,Hepatocytes ,Humans ,Liver ,Lysosomes ,Male ,Mice ,Inbred C57BL ,Mice ,Knockout ,Phosphatidylinositol 4 ,5-Diphosphate ,Phosphoinositide Phosphatases ,Protein Transport ,Proteolysis ,Receptors ,LDL ,Vesicular Transport Proteins ,cholesterol ,lipoprotein ,lysosome ,mice ,phosphatidylinositol ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
ObjectiveTMEM55B (transmembrane protein 55B) is a phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P2) phosphatase that regulates cellular cholesterol, modulates LDLR (low-density lipoprotein receptor) decay, and lysosome function. We tested the effects of Tmem55b knockdown on plasma lipids in mice and assessed the roles of LDLR lysosomal degradation and change in (PI[4,5]P2) in mediating these effects. Approach and Results: Western diet-fed C57BL/6J mice were treated with antisense oligonucleotides against Tmem55b or a nontargeting control for 3 to 4 weeks. Hepatic Tmem55b transcript and protein levels were reduced by ≈70%, and plasma non-HDL (high-density lipoprotein) cholesterol was increased ≈1.8-fold (P
- Published
- 2020