title: 28-Homobrassinolide: a novel oxysterol transactivating LXR gene expression.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Pondicherry University, Pondicherry, 605014, India, prema.srikumar@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Premalatha
authors.forename: K
authors.initials: K
authors.lastname: Srikumar
authors.forename: D
authors.initials: D
authors.lastname: Vijayalaksmi
authors.forename: G N
authors.initials: GN
authors.lastname: Kumar
authors.forename: P P
authors.initials: PP
authors.lastname: Mathur
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002778:Cholestanones / Q000737:chemistry / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D010937:Plant Growth Regulators / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
chemical_list: D002778:Cholestanones; D017931:DNA Primers; D018076:DNA, Complementary; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D010937:Plant Growth Regulators; D013739:Testosterone; C070163:homobrassinolide
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