title: Synthetic High-Density Lipoprotein-Like Nanocarrier Improved Cellular Transport of Lysosomal Cholesterol in Human Sterol Carrier Protein-Deficient Fibroblasts.
abstract: Sterol carrier protein-2 (SCP-2), which is not found in tissues of people with Zellweger syndrome, facilitates the movement of cholesterol within cells, resulting in abnormal accumulation of cholesterol in SCP-2-deficient cells. This study investigated whether synthetic high-density lipoprotein-like nanocarrier (sHDL-NC) improves the cellular transport of lysosomal cholesterol to plasma membrane in SCP-2-deficient fibroblasts. Human SCP-2-deficient fibroblasts were incubated with [(3)H-cholesterol]LDL as a source of cholesterol and sHDL-NC. The cells were fractionated by centrifugation permit tracking of [(3)H]-cholesterol from lysosome into plasma membrane. Furthermore, cellular content of cholesteryl ester as a storage form and mRNA expression of low-density lipoprotein (LDL) receptor were measured to support the cholesterol transport to plasma membrane. Incubation with sHDL-NC for 8 h significantly increased uptake of [(3)H]-cholesterol to lysosome by 53% and further enhanced the transport of [(3)H]-cholesterol to plasma membrane by 32%. Treatment with sHDL-NC significantly reduced cellular content of cholesteryl ester and increased mRNA expression of LDL receptor (LDL-R). In conclusion, sHDL-NC enables increased transport of lysosomal cholesterol to plasma membrane. In addition, these data were indirectly supported by decreased cellular content of cholesteryl ester and increased gene expression of LDL-R. Therefore, sHDL-NC may be a useful vehicle for transporting cholesterol, which may help to prevent accumulation of cholesterol in SCP-2-deficient fibroblasts.
authors.affiliation: Department of Medical Nutrition, Kyung Hee University , Gyeonggi, Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Nam
authors.affiliation: Department of Medical Nutrition, Kyung Hee University , Gyeonggi, Korea.
authors.forename: Ok-Kyung
authors.initials: OK
authors.lastname: Kim
authors.affiliation: Department of Medical Nutrition, Kyung Hee University , Gyeonggi, Korea.
authors.forename: Yoo Kyoung
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Medical Nutrition, Kyung Hee University , Gyeonggi, Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C072087:sterol carrier proteins; D002784:Cholesterol
keywords: LDL receptor; SCP-2; cholesterol; sHDL-NC