Interferon‐γ decreases ATP‐binding cassette subfamily G member 1‐mediated cholesterol efflux through small ubiquitin‐like modifier/ubiquitin‐dependent liver X receptor‐α degradation in macrophages

2020 ◽  
Author(s):  
Mengya Dong ◽  
Yan Zhang ◽  
Chenbo Xu ◽  
Chen Wang ◽  
Mengping Liu ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Interferon Γ ◽  
Liver X Receptor ◽  
Atp Binding ◽  
Liver X Receptor Α ◽  
Atp Binding Cassette

scholarly journals Dichlorodiphenyltrichloroethane Impairs Amyloid Beta Clearance by Decreasing Liver X Receptor α Expression

2021 ◽  
Vol 13 ◽  
Author(s):  
Dongmei Wu ◽  
Yang Hu ◽  
Min Song ◽  
Gongbo Li
Keyword(s):  
Amyloid Beta ◽  
Critical Role ◽  
Liver X Receptor ◽  
Dynamics Simulation ◽  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
Liver X Receptor Α ◽  
Aβ Clearance ◽  
Atp Binding Cassette

Abnormal amyloid beta (Aβ) clearance is a distinctive pathological mechanism for Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), which mediates the lipidation of apolipoprotein E, plays a critical role in Aβ clearance. As an environmental factor for AD, dichlorodiphenyltrichloroethane (DDT) can decrease ATP-binding cassette transporter A1 (ABCA1) expression and disrupt Aβ clearance. Liver X receptor α (LXRα) is an autoregulatory transcription factor for ABCA1 and a target of some environmental pollutants, such as organophosphate pesticides. In this study, we aimed to investigate whether DDT could affect Aβ clearance by targeting LXRα. The DDT-pretreated H4 human neuroglioma cells and immortalized astrocytes were incubated with exogenous Aβ to evaluate Aβ consumption. Meanwhile, cytotoxicity and LXRα expression were determined in the DDT-treated cells. Subsequently, the antagonism of DDT on LXRα agonist T0901317 was determined in vitro. The interaction between DDT and LXRα was predicted by molecular docking and molecular dynamics simulation technology. We observed that DDT could inhibit Aβ clearance and decrease the levels of LXRα mRNA and LXRα protein. Moreover, DDT is supposed to strongly bind to LXRα and exert antagonistic effects on LXRα. In conclusion, this study firstly presented that DDT could inhibit LXRα expression, which would contribute to Aβ clearance decline in vitro. It provides an experimental basis to search for potential therapeutic targets of AD.

scholarly journals Liver X Receptor β (LXRβ) Interacts Directly with ATP-binding Cassette A1 (ABCA1) to Promote High Density Lipoprotein Formation during Acute Cholesterol Accumulation

2011 ◽  
Vol 286 (22) ◽  
pp. 20117-20124 ◽  
Author(s):  
Masako Hozoji-Inada ◽  
Youichi Munehira ◽  
Kohjiro Nagao ◽  
Noriyuki Kioka ◽  
Kazumitsu Ueda
Keyword(s):  
Translational Regulation ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Transcriptional Response ◽  
Liver X Receptor ◽  
Cholesterol Homeostasis ◽  
Atp Binding ◽  
Transcriptional Level ◽  
Cholesterol Accumulation ◽  
Atp Binding Cassette

Cells have evolved multiple mechanisms for maintaining cholesterol homeostasis, and, among these, ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux is highly regulated at the transcriptional level through the activity of the nuclear receptor liver X receptor (LXR). Here, we show that in addition to its well defined role in transcription, LXRβ directly binds to the C-terminal region (2247LTSFL2251) of ABCA1 to mediate its post-translational regulation. In the absence of cholesterol accumulation in the macrophage-like cell line THP-1, the ABCA1-LXRβ complex stably localizes to the plasma membrane, but apolipoprotein A-I (apoA-I) binding or cholesterol efflux does not occur. Exogenously added LXR ligands, which mimic cholesterol accumulation, cause LXRβ to dissociate from ABCA1, thus freeing ABCA1 for apoA-I binding and subsequent cholesterol efflux. Photoaffinity labeling experiments with 8-azido-[α-32P]ATP showed that the interaction of LXRβ with ABCA1 inhibits ATP binding by ABCA1. This is the first study to show that a protein-protein interaction with the endogenous protein suppresses the function of ABC proteins by inhibiting ATP binding. LXRβ can cause a post-translational response by binding directly to ABCA1, as well as a transcriptional response, to maintain cholesterol homeostasis.

Kiwifruit supplementation increases the gene expression of ATP-binding cassette transporter A1 and Liver X receptor α in liver and intestine of hamsters fed with high-fat diet

2021 ◽  
pp. 1-10
Author(s):  
Saba Moradi ◽  
Heidar Tavilani ◽  
Massoud Saidijam ◽  
Mohammad Hashemnia ◽  
Asad Vaisi-Raygani
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Cholesterol Efflux ◽  
Liver X Receptor ◽  
Atp Binding ◽  
Chow Diet ◽  
High Fat ◽  
Abca1 Gene ◽  
Atp Binding Cassette Transporter ◽  
Liver X Receptor Α

BACKGROUND: Liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) as a lipid transporter play an important role in cholesterol efflux from cells. OBJECTIVE: This study was aimed to determine the effect of kiwifruit supplementation on LXRα and ABCA1 gene expressions in liver and intestine of hamsters fed with high-fat diet (HFD). METHODS: 36 Golden Syrian male hamsters were divided into 6 groups (n = 6) including, group 1 received chow diet (control normal), group 2 and 3 received chow diet plus 1.86 and 3.73 g/kg kiwifruit, group 4 received HFD, group 5 and 6 received HFD plus 1.86 and 3.73 g/kg kiwifruit for 8 weeks. RESULTS: ABCA1 gene expression were significantly decreased in the liver (p <  0.01) and the intestine (p <  0.05) of HFD group compared with control normal. The gene expression levels of ABCA1 from liver and intestine were increased in HFD treated with kiwifruit compare to untreated HFD group (p <  0.05). LXRα gene expression of intestine was increased in all of the kiwifruit treated groups compared with untreated groups (p <  0.05). CONCLUSIONS: Consumption of kiwifruit in in hamsters receiving HFD can improve cholesterol efflux from liver and intestine by increase the gene expression of ABCA1 and LXRα.

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