Effect of activation of liver X receptor alpha on cardiac & hepatic ABCC10 and SLC17A5 drug transporters in hypercholesterolemic rat model
Copyright © 2022 Elsevier Inc. All rights reserved..
BACKGROUND: Liver x receptor α (LXRα) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. Oxysterols (endogenous oxidized cholesterol derivatives) are the most potent endogenous LXRα-agonist. LXRα has a direct impact on several members of drug transporter superfamilies; ATP-binding cassette (ABC) and solute linked carrier (SLC).
OBJECTIVE: The current study aimed to investigate the effect of LXRα-activation by either endogenous oxysterols or a synthetic LXRα-agonist (LXRa) such as TO901317 on hepatic and cardiac gene expression of ABCC10 and SLC17A5 drug transporters in an experimentally hypercholesterolemic rat model.
METHODS: 48 male rats were divided randomly into four groups (n = 12); control group rats received vehicle; hypercholesterolemic group (HCH group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks; (LXRa group) rats were fed standard pellet chow for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg; (HCH + LXRa group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg.
RESULTS: Our findings revealed that hypercholesterolemia and LXRa significantly activated LXRα to varying degrees in both hepatic and cardiac tissues with subsequent alteration of LXRα and ABCC10 gene expression. Whereas, SLC17A5 gene expression was primarily affected by elevated serum cholesterol level and unmediated via LXRα-activation.
CONCLUSIONS: Accordingly, it was concluded that ABCC10 is a specific LXRα-target gene and that LXRα autoregulates its own expression in rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:610 |
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| Enthalten in: |
Biochemical and biophysical research communications - 610(2022) vom: 25. Juni, Seite 133-139 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
El-Ashmawy, Nahla E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2022 Date Revised 26.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2022.04.046 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM339912073 |
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| 100 | 1 | |a El-Ashmawy, Nahla E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of activation of liver X receptor alpha on cardiac & hepatic ABCC10 and SLC17A5 drug transporters in hypercholesterolemic rat model |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 26.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Liver x receptor α (LXRα) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. Oxysterols (endogenous oxidized cholesterol derivatives) are the most potent endogenous LXRα-agonist. LXRα has a direct impact on several members of drug transporter superfamilies; ATP-binding cassette (ABC) and solute linked carrier (SLC) | ||
| 520 | |a OBJECTIVE: The current study aimed to investigate the effect of LXRα-activation by either endogenous oxysterols or a synthetic LXRα-agonist (LXRa) such as TO901317 on hepatic and cardiac gene expression of ABCC10 and SLC17A5 drug transporters in an experimentally hypercholesterolemic rat model | ||
| 520 | |a METHODS: 48 male rats were divided randomly into four groups (n = 12); control group rats received vehicle; hypercholesterolemic group (HCH group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks; (LXRa group) rats were fed standard pellet chow for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg; (HCH + LXRa group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg | ||
| 520 | |a RESULTS: Our findings revealed that hypercholesterolemia and LXRa significantly activated LXRα to varying degrees in both hepatic and cardiac tissues with subsequent alteration of LXRα and ABCC10 gene expression. Whereas, SLC17A5 gene expression was primarily affected by elevated serum cholesterol level and unmediated via LXRα-activation | ||
| 520 | |a CONCLUSIONS: Accordingly, it was concluded that ABCC10 is a specific LXRα-target gene and that LXRα autoregulates its own expression in rats | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ATP-Binding cassette | |
| 650 | 4 | |a Hypercholesterolemia | |
| 650 | 4 | |a Liver x receptor alpha | |
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| 700 | 1 | |a Sallam, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Nossier, Ahmed Ibrahim |e verfasserin |4 aut | |
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