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PMID: 18562560 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Circadian variations in rat liver gene expression: relationships to drug actions.

The Journal of pharmacology and experimental therapeutics ·Vol. 326 ·No. 3 ·2008-09-00 ·Pages 700-16

Almon RR, Yang E, Lai W, Androulakis IP, DuBois DC, Jusko WJ

Abstract

Chronopharmacology is an important but under-explored aspect of therapeutics. Rhythmic variations in biological processes can influence drug action, including pharmacodynamic responses, due to circadian variations in the availability or functioning of drug targets. We hypothesized that global gene expression analysis can be useful in the identification of circadian-regulated genes involved in drug action. Circadian variations in gene expression in rat liver were explored using Affymetrix gene arrays. A rich time series involving animals analyzed at 18 time points within the 24-h cycle was generated. Of the more than 15,000 probe sets on these arrays, 265 exhibited oscillations with a 24-h frequency. Cluster analysis yielded five distinct circadian clusters, with approximately two thirds of the transcripts reaching maximal expression during the dark/active period of the animal. Of the 265 probe sets, 107 were identified as having potential therapeutic importance. The expression levels of clock genes were also investigated in this study. Five clock genes exhibited circadian variation in the liver, and data suggest that these genes may also be regulated by corticosteroids.

MeSH Terms
Animals CLOCK Proteins Circadian Rhythm/drug effects,genetics Corticosterone/blood Gene Expression Regulation/drug effects,genetics Liver/drug effects,physiology Male Pharmaceutical Preparations/administration & dosage Rats Rats, Wistar Trans-Activators/biosynthesis,genetics
Chemicals
Pharmaceutical Preparations Trans-Activators CLOCK Proteins Clock protein, rat Corticosterone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Almon Richard R
Department of Biological Sciences, 107 Hochstetter Hall, State University of New York at Buffalo, Buffalo, NY 14260, USA. [email protected]
Yang Eric
Lai William
Androulakis Ioannis P
DuBois Debra C
Jusko William J
References (39)
39 references, click to expand
  1. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia.
    Blood. 2005 Jul 15;106(2):717-20 PMID: 15797993
  2. Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man.
    Proc Natl Acad Sci U S A. 1982 May;79(9):3037-41 PMID: 6953446
  3. Pharmacogenomic responses of rat liver to methylprednisolone: an approach to mining a rich microarray time series.
    AAPS J. 2005 Aug 18;7(1):E156-94 PMID: 16146338
  4. Chemical genetics approach to identify peptide ligands that selectively stimulate DAPK-1 kinase activity.
    Biochemistry. 2007 Mar 13;46(10):2655-73 PMID: 17297916
  5. Mevalonate metabolism by renal tissue in vitro.
    J Lipid Res. 1974 Jan;15(1):20-5 PMID: 4811213
  6. Molecular basis of intrahepatic cholestasis.
    Ann Med. 2004;36(8):606-17 PMID: 15768832
  7. Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis.
    Oncogene. 2005 Jun 23;24(27):4421-32 PMID: 15856026
  8. When the Clock stops ticking, metabolic syndrome explodes.
    Nat Med. 2006 Jan;12(1):54-5; discussion 55 PMID: 16397568
  9. Biological rhythms in the inflammatory response and in the effects of non-steroidal anti-inflammatory drugs.
    Pharmacol Ther. 1995 May;66(2):285-300 PMID: 7667399
  10. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.
    Nat Genet. 2004 Dec;36(12):1319-25 PMID: 15565110
  11. A microarray analysis of the temporal response of liver to methylprednisolone: a comparative analysis of two dosing regimens.
    Endocrinology. 2007 May;148(5):2209-25 PMID: 17303664
  12. Circadian clocks: neural and peripheral pacemakers that impact upon the cell division cycle.
    Mutat Res. 2005 Jul 1;574(1-2):76-91 PMID: 15914209
  13. Aurora-B regulates RNA methyltransferase NSUN2.
    Mol Biol Cell. 2007 Mar;18(3):1107-17 PMID: 17215513
  14. The days and nights of cancer cells.
    Cancer Res. 2003 Nov 15;63(22):7545-52 PMID: 14633665
  15. In vivo regulation of human mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase. Studies in normal subjects.
    J Clin Invest. 1987 Apr;79(4):1125-32 PMID: 3558818
  16. Genetic clock of biologic rhythms.
    J Cell Mol Med. 2003 Oct-Dec;7(4):408-16 PMID: 14754509
  17. Chaperonin-mediated protein folding: fate of substrate polypeptide.
    Q Rev Biophys. 2003 May;36(2):229-56 PMID: 14686103
  18. Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of beta-tubulins.
    Int J Cancer. 2007 May 15;120(10):2078-85 PMID: 17285590
  19. Aberrant methylation of Reprimo in human malignancies.
    Int J Cancer. 2005 Jul 1;115(4):503-10 PMID: 15700311
  20. Regulation of glucocorticoid receptor steroid binding and trafficking by the hsp90/hsp70-based chaperone machinery: implications for clinical intervention.
    Leukemia. 2005 May;19(5):710-2 PMID: 15759036
  21. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression.
    Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1840-5 PMID: 11701475
  22. Single-injection ornithine decarboxylase-directed antisense therapy using atelocollagen to suppress human cancer growth.
    Cancer. 2007 Mar 1;109(5):993-1002 PMID: 17318877
  23. System-level identification of transcriptional circuits underlying mammalian circadian clocks.
    Nat Genet. 2005 Feb;37(2):187-92 PMID: 15665827
  24. TXR1-mediated thrombospondin repression: a novel mechanism of resistance to taxanes?
    Genes Dev. 2006 Aug 1;20(15):1975-81 PMID: 16882973
  25. Emerging concepts in targeting the polyamine metabolic pathway in epithelial cancer chemoprevention and chemotherapy.
    J Biochem. 2006 Jan;139(1):27-33 PMID: 16428316
  26. Squalene epoxidase as hypocholesterolemic drug target revisited.
    Prog Lipid Res. 2003 Jan;42(1):37-50 PMID: 12467639
  27. Apoptosis factor EI24/PIG8 is a novel endoplasmic reticulum-localized Bcl-2-binding protein which is associated with suppression of breast cancer invasiveness.
    Cancer Res. 2005 Mar 15;65(6):2125-9 PMID: 15781622
  28. Circulating tumoral cells lack circadian-rhythm in hospitalized metastasic breast cancer patients.
    Clin Transl Oncol. 2006 Nov;8(11):826-9 PMID: 17134972
  29. Analysis of methylprednisolone, methylprednisone and corticosterone for assessment of methylprednisolone disposition in the rat.
    J Chromatogr. 1988 Sep 9;430(2):241-8 PMID: 3235500
  30. Enzyme immunoassay of urinary mevalonic acid and its clinical application.
    Clin Chem. 1998 Oct;44(10):2152-7 PMID: 9761249
  31. The application of HSP70 as a target for gene therapy.
    Front Biosci. 2006 Jan 01;11:699-707 PMID: 16146762
  32. Clinical chronobiology and chronotherapeutics with applications to asthma.
    Chronobiol Int. 1999 Sep;16(5):539-63 PMID: 10513882
  33. eIF4A3 is a novel component of the exon junction complex.
    RNA. 2004 Feb;10(2):200-9 PMID: 14730019
  34. Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors.
    Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S125-35 PMID: 17259553
  35. In vivo regulation of human mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase. Decreased enzyme catalytic efficiency in familial hypercholesterolemia.
    J Clin Invest. 1987 Nov;80(5):1401-8 PMID: 2824560
  36. Phenotype of Per1- and Per2-expressing neurons in the suprachiasmatic nucleus of a diurnal rodent (Arvicanthis ansorgei): comparison with a nocturnal species, the rat.
    Cell Tissue Res. 2002 Oct;310(1):85-92 PMID: 12242487
  37. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes.
    J Biol Chem. 2003 Oct 17;278(42):41519-27 PMID: 12865428
  38. Concepts in chronopharmacology.
    Annu Rev Pharmacol Toxicol. 1992;32:51-66 PMID: 1605576
  39. Synchronization of the molecular clockwork by light- and food-related cues in mammals.
    Biol Chem. 2003 May;384(5):711-9 PMID: 12817467
Article Info
Journal
The Journal of pharmacology and experimental therapeutics
Abbr.
J Pharmacol Exp Ther
ISSN
1521-0103
DOI
10.1124/jpet.108.140186
Email
[email protected]
Published
2008-09-00
Epub
2008-00-18
Pages
700-16
Language
English
Region
United States
NLM ID
0376362
PMCID
PMC2561907
Subset
IM
Grants
NIGMS NIH HHS · R37 GM024211 · United States
NHLBI NIH HHS · U01 HL066614 · United States
NIGMS NIH HHS · R01 GM082974-02 · United States
NIGMS NIH HHS · R01 GM024211 · United States
NIGMS NIH HHS · R01 GM082974-01A2 · United States
NHLBI NIH HHS · HL 66614 · United States
NIGMS NIH HHS · GM 24211 · United States
NIGMS NIH HHS · R01 GM082974 · United States
NIGMS NIH HHS · R37 GM024211-31 · United States
External Links
PubMed source DOI: 10.1124/jpet.108.140186 PMC Full Text View journal details
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