28-Homobrassinolide: a Novel Oxysterol Transactivating LXR Gene Expression

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2014 Aug 6

PMID 25091941

Citations 2

Authors

R Premalatha

K Srikumar

D Vijayalaksmi

G N Kumar

P P Mathur

Affiliations

Soon will be listed here.

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.

Citing Articles

Nuclear Receptors and Lipid Sensing.

Thorne J, Cioccoloni G Adv Exp Med Biol. 2022; 1390:83-105.

PMID: 36107314 DOI: 10.1007/978-3-031-11836-4_5.

A plant oxysterol, 28-homobrassinolide binds HMGCoA reductase catalytic cleft: stereoselective avidity affects enzyme function.

Mukherjee V, Vijayalaksmi D, Gulipalli J, Premalatha R, Sufi S, Velan A Mol Biol Rep. 2016; 43(10):1049-58.

PMID: 27585573 DOI: 10.1007/s11033-016-4052-5.

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