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28-Homobrassinolide: a novel oxysterol transactivating LXR gene expression

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Abstract

Cholesterol is the template for steroid hormone biosynthesis. Cholesterol homeostasis is regulated by Cyt-P450 oxygenated cholesterols acting as ligands on LXR-α and LXR-β transcription factors that are now emerging as drug targets. Heterodimerization of LXRs with retinoic acid receptor is considered a prerequisite for target gene activation. Dietary plant oxysterol 28-homobrassinolide (28-HB) is a proven antihyperglycemic and a pro-steroidogenic agent in the rat. Whether 28-HB has a role in LXR gene expression was therefore investigated using oral gavage (15 days) of 28-HB (333 µg/kg b w) to normal and diabetic rat. PCR amplified LXR-α and β mRNA transcripts from treated rat liver and testis exhibited quantitative differences in their expression. Conformational differences in 28-HB docking to LXR-α and β binding domains were also noted through in silico studies, LXR-β adopting lesser specificity. We report that 28-HB transactivates LXR genes in the rat tissues.

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Acknowledgments

The authors gratefully acknowledge the financial support received from University Grants Commission, New Delhi, Department of Science and Technology, Government of India, UGC-SAP, DBT-IPLS and DST-FIST programs. P. P. Mathur acknowledges the Government of India, Department of Biotechnology, BT/BI/03/015/2002, and Department of Information Technology, DIT/R&D/BIO/15(9)/2007. RP gratefully acknowledges Technical help received from N. Selvaraj, Department of Biochemistry, Sri Venkateshwaraa Medical College Hospital and Research Centre, Pondicherry, V. Athithan and R. Jubendradass of Department of Biochemistry & Molecular Biology, Pondicherry University.

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  1. P. P. Mathur

    Present address: KIIT University, Bhubaneswar, 751024, Odisha, India

Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Pondicherry University, Pondicherry, 605014, India

    R. Premalatha, K. Srikumar, G. N. Kumar & P. P. Mathur

  2. School of Life Sciences, Center for Bioinformatics, Pondicherry University, Pondicherry, 605014, India

    D. Vijayalaksmi & P. P. Mathur

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  1. R. Premalatha
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Premalatha, R., Srikumar, K., Vijayalaksmi, D. et al. 28-Homobrassinolide: a novel oxysterol transactivating LXR gene expression. Mol Biol Rep 41, 7447–7461 (2014). https://doi.org/10.1007/s11033-014-3632-5

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