28-Homobrassinolide: a novel oxysterol transactivating LXR gene expression
详细信息    查看全文
  • 作者:R. Premalatha (1)
    K. Srikumar (1)
    D. Vijayalaksmi (2)
    G. N. Kumar (1)
    P. P. Mathur (1) (2) (3)
  • 关键词:28 ; Homobrassinolide (28 ; HB) ; Plant oxysterol ; 28 ; HB ; LXR interactions ; LXR ; α expression ; LXR ; β expression
  • 刊名:Molecular Biology Reports
  • 出版年:2014
  • 出版时间:November 2014
  • 年:2014
  • 卷:41
  • 期:11
  • 页码:7447-7461
  • 全文大小:3,013 KB
  • 参考文献:1. Lund E, Bjoerkhem I (1995) Role of oxysterols in the regulation of cholesterol homeostasis: a critical evaluation. Acc Chem Res 28:241-49 CrossRef
    2. Janowski BA, Willy PJ, Devi TR et al (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728-31 CrossRef
    3. Ryan KK, Seeley RJ (2013) Food as a hormone. Science 339:918-19 CrossRef
    4. Verger PH, LeBlanc JC (2003) Concentration of phytohormones in food and feed and their impact on the human exposure. Pure Appl Chem 75:1873-880 CrossRef
    5. Muthuraman P, Srikumar K (2007) A brassinosteroid as an antihyperglycemic in alloxan induced diabetic rats. J Curr Sci 9:22-8
    6. Muthuraman P, Ravikumar S, Vikramathithan J, Nirmalkumar G, Srikumar K (2010) Effect of phytohormones on tissue hexokinase and on some blood components in wistar rats. Int J Drug Deliv 2:168-72 CrossRef
    7. Premalatha R, Jubendradass R, Rani SJ et al (2013) A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in normal and diabetic rats. Reprod Sci 20:589-96 CrossRef
    8. Bergstrom S, Wintersteiner O (1941) Autoxidation of sterols in colloidal aqueous solution: the nature of the products formed from cholesterol. J Biol Chem 141:597-10
    9. Schultz JR, Tu H, Luk A et al (2000) Role of LXRs in control of lipogenesis. Genes Dev 14:2831-838 CrossRef
    10. Collins JL, Fivush AM, Watson MA et al (2002) Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem 45:1963-966 CrossRef
    11. Laffitte BA, Chao LC, Li J et al (2003) Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 100:5419-424 CrossRef
    12. Venkateswaran A, Laffitte BA, Joseph SB et al (2000) Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA 97:12097-2102 CrossRef
    13. Im SS, Osborne TF (2011) Liver X receptors in atherosclerosis and inflammation. Circ Res 108:996-001 CrossRef
    14. Joseph SB, Castrillo A, Laffitte BA et al (2003) Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 9:213-19 CrossRef
    15. Lehmann JM, Kliewer SA, Moore LB et al (1997) Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem 272:3137-140 CrossRef
    16. Sparrow CP, Baffic J, Lam MH et al (2002) A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. J Biol Chem 277:10021-0027 CrossRef
    17. Shen Q, Bai Y, Chang KC et al (2011) Liver X receptor-retinoid X receptor (LXR-RXR) heterodimer cistrome reveals coordination of LXR and AP1 signaling in keratinocytes. J Biol Chem 286:14554-4563 CrossRef
    18. Svensson S, Ostberg T, Jacobsson M et al (2003) Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation. EMBO J 22:4625-633
文摘
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.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700