Rapamycin pre-treatment abrogates Tumour Necrosis Factor-α down-regulatory effects on LXR-α and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells
Document title: Rapamycin pre-treatment abrogates Tumour Necrosis Factor-α down-regulatory effects on LXR-α and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells
Journal: Electronic journal of biotechnology
Database: PERIÓDICA
System number: 000398050
ISSN: 0717-3458
Authors: 1
2
1
2
3
1
2
Institutions: 1Universiti Tunku Abdul Rahman, Faculty of Science, Kampar, Perak. Malasia
2Universiti Tunku Abdul Rahman, Department of Biomedical Sciences, Kampar, Perak. Malasia
3Universiti Malaysia Terengganu, Faculty of Science and Technology, Terengganu. Malasia
Year:
Volumen: 14
Number: 3
Pages: 1-11
Country: Chile
Language: Inglés
Document type: Artículo
Approach: Analítico, descriptivo
English abstract The Liver X Receptor (LXR) and Pregnane X Receptor (PXR) are members of the nuclear receptor superfamily. Previously, they have been classified as important regulators of lipid homeostasis. However, recent studies have shown that they may be implicated in anti-inflammatory responses as well. This study shows that Tumour Necrosis Factor - α (TNF - α ) treatment reduces both LXR - α and PXR mRNA expression. However, pre -treatment with rapamycin, an mTOR inhibitor, followed by TNF - α stimulation, significantly induces LXR - α and PXR mRNA expression to ~17- and ~2 - fold, respectively. This suggests that mTORC1, a multi -molecular complex of which mTOR is a member, may act as a negative regulator that inhibits the induction of LXR - α and PXRas anti - inflammatory genes. It is also shown here that inhibition of JNK1 via the mTOR/Akt pathway coincides with the up- regulation of LXR - α and PXR mRNA, after TNF - α treatment. Together, these observat ions suggest that JNK1 possibly act downstream of mTORC1 as an LXR - α and PXR inhibitor. From the results gleaned in this study, rapamycin (and its analogues) may be used to reduce acute inflammation by promoting the induction of LXR - α and PXR as anti-inflammatory genes
Disciplines: Biología,
Química,
Medicina
Keyword: Genética,
Bioquímica,
Metabolismo y nutrición,
Cinasa Akt,
Factor de necrosis tumoral,
Homeostasis,
Inflamación,
Tratamiento,
Factor de transcripción
Keyword: Biology,
Chemistry,
Medicine,
Genetics,
Biochemistry,
Metabolism and nutrition,
Akt kinase,
Tumor necrosis factor,
Homeostasis,
Inflammation,
Treatment,
Transcription factor
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