27-Hydroxycholesterol regulates cholesterol synthesis and transport in C6 glioma cells.
The oxysterol 27-Hydroxycholesterol (27-OHC) is a major cholesterol metabolite that can cross the blood brain barrier (BBB) from peripheral circulation to the brain. Currently, the role of 27-OHC on cholesterol homeostasis in astrocytes and the underlying mechanisms are not defined. Since all brain cholesterol is essentially synthesized in brain itself and astrocytes as net producers of cholesterol are essential for normal brain function, here we investigated the effects of 27-OHC on cholesterol synthesis and transport in C6 glioma cells. C6 cells were treated with 5, 10 and 20μM 27-OHC for 24h and the cell viability and apoptosis, the cholesterol levels and metabolism-related mediators, genes and proteins were subsequently assessed using cell-counting kit (CCK)-8, Amplex red, ELISA, real-time PCR and Western blot, respectively. We found that 27-OHC decreased cholesterol levels by down-regulating the expression of sterol-regulated element binding protein-1 (SREBP-1a), 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDLR) and promoted cholesterol transport by up-regulating the expression of peroxisome proliferator-activated receptors-γ (PPAR-γ), liver X receptor-α (LXR-α), ATP-binding cassette transporter protein family member A1 (ABCA1) and apolipoprotein E (ApoE)genes. Our results suggested that 27-OHC may represent a sensitive modulator of cholesterol metabolism disorder by suppressing cholesterol synthesis and stimulating cholesterol transport in astrocytes.
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Yu
Y
An
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Department of Nutrition, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing 101149, China.
Dan-Di
DD
Zhang
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Huan-Ling
HL
Yu
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Wei-Wei
WW
Ma
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Yan-Hui
YH
Lu
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Quan-Ri
QR
Liu
School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: xiaor22@ccmu.edu.cn.
Rong
R
Xiao
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005372:Filipin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000473:pathology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013997:Time Factors
D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D011973:Receptors, LDL; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C076996:27-hydroxycholesterol; D005372:Filipin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases
27-hydroxycholesterol; Astrocyte; Brain; Cholesterol; Synthesis; Transport