Skip to main content
SpringerLink
Log in

Pharmacodynamics and Pharmacogenomics of Diverse Receptor-Mediated Effects of Methylprednisolone in Rats Using Microarray Analysis

  • Published:
Journal of Pharmacokinetics and Pharmacodynamics Aims and scope Submit manuscript

Abstract

Corticosteroids such as methylprednisolone (MPL) produce many of their anti-inflammatory, immunosuppressive, and exaggerated physiological effects by receptor and gene-mediated mechanisms. The temporal pattern of change in four genes in rat tissues was measured by quantitative Northern hybridization and rtPCR after a single dose of MPL. Two profiles were observed: two genes with enhanced expression showed a slow onset and moderate rate of decline within a 24 hr time frame while two genes with reduced expression exhibited a rapid onset and prolonged suppression over a ≥ 72 hr time span. These patterns are consistent with and rationalized by pharmacodynamic expectations based on earlier models. cDNA microarrays used to assess the expression levels of 5200 genes at one optimal time-point showed marked variation in baseline values. Of these, 20 genes showed statistically significant enhanced expression with increases ranging from 130 to 1690%, 31 genes exhibited reduced expression ranging from 31 to 72% of control. Many genes could be categorized as affecting acute phase/immune response, energy metabolism, microsomal metabolism, and hepatic function. These studies provide the first simultaneous assessment of the diversity in pharmacogenomic effects of corticosteroids. They also provide some insight into the advantages and limitations of microarray measurements in regard to the pharmacodynamics of drugs having complex, multi-faceted, and integrated mechanisms of action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. A. G. Frauman. An overview of the adverse reactions to adrenal corticosteroids. Adverse Drug React. Toxicol. Rev. 15:203-206 (1996).

    PubMed  Google Scholar 

  2. J. M. Goust, H. Stevenson, R. Galbraith, and G. Virella. Immunosuppression and immunomodulation. Immunology Ser. 58:465-480 (1993).

    Google Scholar 

  3. L. Locsey, L. Asztalos, Z. Kincses, F. Gyorfi, and C. Berczi. Dyslipidaemia and hyperlipidaemia following renal transplantation. Intern. Urol. Nephrol. 28:419-430 (1996).

    Google Scholar 

  4. S. Gluecksohn-Waelsch. Developmental genetics of hepatic gluconeogenic enzymes. Ann. N.Y. Acad. Sci. 478:101-108 (1986).

    PubMed  Google Scholar 

  5. D. G. Sapir, T. Pozefsky, J. P. Knochel, and M. Walser. The role of alanine and glutamine in steroid-induced nitrogen wasting in man. Clin. Sci. Molec. Med. 53:215-220 (1977).

    Google Scholar 

  6. Y. N. Sun, L. I. McKay, D. C. DuBois, W. J. Jusko, and R. R. Almon. Pharmacokinetic_ Pharmacodynamic models for corticosteroid receptor down-regulation and glutamine synthetase induction in rat skeletal muscle by a receptor_gene-mediated mechanism. J. Pharmaco. Exper. Therap. 288:720-728 (1999).

    Google Scholar 

  7. M. McMahon, J. Gerich, and R. Rizza. Effects of glucocorticoids on carbohydrate metabolism. Diabetes-Metabolism Rev. 4:17-30 (1988).

    Google Scholar 

  8. R. C. Andrews and B. R. Walker. Glucocorticoids and insulin resistance: old hormones, new targets. Clin.Sci. 96:513-523 (1999).

    PubMed  Google Scholar 

  9. E. F. Morand and M. Leech. Glucocorticoid regulation of inflammation: the plot thickens. Inflam. Res. 48:557-560 (1999).

    Google Scholar 

  10. B. H. Pannen and J. L. Robotham. The acute-phase response. New Hor. 3:183-197 (1995).

    Google Scholar 

  11. C. D. Berdanier. Role of glucocorticoids in the regulation of lipogenesis. FASEB Journ. 3:2179-2183 (1989).

    Google Scholar 

  12. R. A. Prough, M. W. Linder, J. A. Pinaire, G. H. Xiao, and K. C. Falkner. Hormonal regulation of hepatic enzymes involved in foreign compound metabolism. FASEB Journ. 10:1369-1377 (1996).

    Google Scholar 

  13. W. F. Ebling, S. J. Szefler, and W. J. Jusko, Methylprednisolone disposition in rabbits: analsysis, prodrug conversion, reversible metabolism and comparison with man. Drug Metab. Dispos. 13:296-304 (1985).

    PubMed  Google Scholar 

  14. P. Chomczynski and N. Sacchi. Single-step method of RNA isolation by acid guanidinium thiocyornate-phenol-chloroform extraction. Anal. Biochem. 162:156-159 (1987).

    PubMed  Google Scholar 

  15. B. Han, D. C. DuBois, K. M. K. Boje, S. J. Free, and R. R. Almon. Quantification of iNOS mRNA with reverse transcription polymerase chain reaction directly from cell lysates. NITRIC OXIDE: Biol. Chem. 3:281-291 (1999).

    Google Scholar 

  16. D. C. DuBois, Z. X. Xu, L. McKay, R. R. Almon, N. Pyszcznski, and W. J. Jusko. Differential dynamics of receptor down-regulation and tyrosine aminotransferase induction following glucocorticoid treatment. J. Ster. Biochem. Mol. Biol. 54:237-243 (1995).

    Google Scholar 

  17. Y.-N. Sun, D. C. DuBois, R. R. Almon, and W. J. Jusko. Fourth-generation model for corticosteroid pharmacodynamics: A model for methylprednisolone effects on receptor_ gene-mediated glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver. J. Pharmacokin. Biopharm. 26:289-317 (1998).

    Google Scholar 

  18. Z. X. Xu, Z. X., Y. N. Sun, D. C. DuBois, R. R. Almon, and W. J. Jusko. Thirdgeneration model for corticosteroid pharmacodynamics: roles of glucocorticoid receptor mRNA and tyrosine aminotransferase mRNA in rat liver. J. Pharmacokin. Biopharm. 23:163-181 (1995).

    Google Scholar 

  19. C. Jux, K. Leiber, U. Hugel, W. Blum, C. Ohlsson, G. Klaus, and O. Mehls. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH-and IGF-I-receptor in cultured rat chondrocytes. Endocrinol. 139:3296-305 (1998).

    Google Scholar 

  20. J. M. Luo and L. J. Murphy. Dexamethasone inhibits growth hormone induction of insulin-like growth factor-I (IGF-I) messenger ribonucleic acid (mRNA) in hypophysectomized rats and reduces IGF-I mRNA abundance in the intact rat. Endocrinol. 125:165-171 (1989).

    Google Scholar 

  21. K. Binz, C. Schmid, R. Bouillon, E. R. Froesch, K. Jurgensen, and E. B. Hunziker. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur. Journ. Endocrinol. 130:387-393 (1994).

    Google Scholar 

  22. T. S. Juan, D. R. Wilson, M. D. Wilde, and G. J. Darlington. Participation of the transcription factor C_EBP delta in the acute-phase regulation of the human gene for complement component C3. Proc. Nat. Acad. Sci. U.S.A. 90:2584-2588 (1993).

    Google Scholar 

  23. S. Kumar, C. Mitnik, G. Valente, and G. Floyd-Smith. Expansion and molecular evolution of the interferon-induced 2'-5' oligoadenylate synthetase gene family. Mol. Biol. Evol. 17:738-750 (2000).

    PubMed  Google Scholar 

  24. M. Watanabe, M. Yagi, M. Omata, N. Hirasawa, S. Mue, S. Tsurufuji, and K. Ohuchi. Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone. Br. J. Pharm. 102:239-245 (1991).

    Google Scholar 

  25. A. Gouin-Charnet, D. Laune, C. Granier, J. C. Mani, B. Pau, G. Mourad, and A. Argiles. Alpha2-macroglobulin, the main serum antiprotease, binds beta2-microglobulin, the light chain of the class I major histocompatibility complex, which is involved in human disease. Clin. Sci. 98:427-433 (2000).

    PubMed  Google Scholar 

  26. J. P. Rabek and J. Papaconstantinou. Interference mapping of nuclear protein binding to the acute phase response element of the mouse alpha1-acid glycoprotein gene. Biochem. Biophys. Res. Commun. 255:608-13 (1999).

    PubMed  Google Scholar 

  27. M. M. Van Den Heuvel, D. C. Poland, C. S. De Graaff, E. C. Hoefsmit, P. E. Postmus, R. H. Beelen, and W. Van Dijk. The degree of branching of the glycans of alpha(1)-acid glycoprotein in asthma. A correlation with lung function and inflammatory parameters. Am. J. Respir. Crit. Care Med. 161:1972-1978 (1972).

    Google Scholar 

  28. J. G. Haddad. Plasma vitamin D-binding protein (Gc-globulin): multiple tasks. J. Ster. Biochem. Mol. Biol. 53:579-582 (1995).

    Google Scholar 

  29. C. J. de Haas. New insights into the role of serum amyloid P component, a novel lipopolysaccharide-binding protein. FEMS Immunol. Med. Microbiol. 26:197-202 (1999).

    PubMed  Google Scholar 

  30. D. M. Fowlkes, N. T. Mullis, C. M. Comeau, and G. R. Crabtree. Potential basis for regulation of the coordinately expressed fibrinogen genes: homology in the 5' flanking regions. Proc. Nat. Acad. Sci. U.S.A. 81:2313-2316 (1984).

    Google Scholar 

  31. F. Iwasa, S. Sassa, and A. Kappas. The effects of acute phase inducers and dimetylsphoxide on delta-aminolaevulinate synthetase activity in human HepG2 hepatoma cells. Biochem. J. 15:605-607 (1989).

    Google Scholar 

  32. M. Nordberg and G. F. Nordberg. Toxicological aspects of metallothionein. Cell. Mol. Biol. 46:451-63 (2000).

    Google Scholar 

  33. M. C. Jong, J. H. van Ree, V. E. Dahlmans, R. R. Frants, M. H. Hofker, and L. M. Havekes. Reduced very-low-density lipoprotein fractional catabolic rate in apolipoprotein C1-deficient mice. Biochem. J. 321:445-50 (1997).

    PubMed  Google Scholar 

  34. J. B. Swaney and K. H. Weisgraber. Effect of apolipoprotein C-I peptides on the apolipoprotein E content and receptor-binding properties of beta-migrating very low density lipoproteins. J. Lip. Res. 35:134-42 (1994).

    Google Scholar 

  35. D. J. Rader and C. Maugeais. Genes influencing HDL metabolism: new perspectives and implications for atherosclerosis prevention. Mol. Med. Today 6:170-5 (2000).

    PubMed  Google Scholar 

  36. C. J. Fielding and P. E. Fielding. Molecular physiology of reverse cholesterol transport. J. Lip.Res. 36:211-228 (1995).

    Google Scholar 

  37. J. A. Beentjes, A. van Tol, W. J. Sluiter, and R. P. Dullaart. Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy. Scand. J. Clin. Lab. Invest. 60:189-198 (2000).

    PubMed  Google Scholar 

  38. J. Gartner, G. Jimenez-Sanchez, P. Roerig, and D. Valle. Genomic organization of the 70-kDa peroxisomal membrane protein gene (PXMP1). Genom. 48:203-208 (1998).

    Google Scholar 

  39. P. Letteron, N. Brahimi-Bourouina, M. A. Robin, A. Moreau, G. Feldmann, and D. Pessayre. Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation. Am. J. Physiol. 272:G1141-1150 (1997).

    PubMed  Google Scholar 

  40. D. L. Kroetz, P. Yook, P. Costet, P. Bianchi, and T. Pineau. Peroxisome proliferatoractivated receptor alpha controls the hepatic CYP4A induction adaptive response to starvation and diabetes. J. Biol. Chem. 273:31581-31589 (1998).

    PubMed  Google Scholar 

  41. O. Sabzevari, M. Hatcher, P. Kentish, O. Sullivan, and G. G. Gibson. Bifonazole, but not the structurally-related clotrimazole, induces both peroxisome proliferation and members of the cytochrome P4504A sub-family in rat liver. Toxicology 106:19-26 (1996).

    PubMed  Google Scholar 

  42. K. J. Woodcroft and R. F. Novak. Insulin differentially affects xenobiotic-enhanced cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes. J. Pharmacol. Experim. Therap. 289:1121-1127 (1999).

    Google Scholar 

  43. M. P. Sowden, H. L. Collins, H. C. Smith, T. A. Garrow, J. D. Sparks, and C. E. Sparks. Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase. Biochem. J. 341:639-645 (1999).

    PubMed  Google Scholar 

  44. J. T. Brosnan. Glutamate, at the interface between amino acid and carbohydrate metabolism. J. Nutr. 130:988S-990S (2000).

    PubMed  Google Scholar 

  45. I. Nissim, M. E. Brosnan, M. Yudkoff, and J. T. Brosnan. Studies of hepatic glutamine metabolism in the perfused rat liver with (15)N-labeled glutamine. J. Biol. Chem. 274:28958-28965 (1999).

    PubMed  Google Scholar 

  46. K. A. Orfali and M. C. Sugden. Modulation of hepatic pyruvate dehydrogenase kinase (PDHK) activity by insulin and dietary composition. Biochem. Soc. Transact. 25:103S (1997).

    Google Scholar 

  47. E. Shafrir and M. Orevi. Response of hepatic fructokinase to long-term sucrose diets and diabetes in spiny mice, albino mice and rats. Compar. Biochem. Physiol. B: Compar. Biochem. 78:493-498 (1984).

    Google Scholar 

  48. M. A. Argiriadi, C. Morisseau, B. D. Hammock, and D. W. Christianson. Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase. Proc. Nat. Acad. Sci. U.S.A. 96:10637-10642 (1999).

    Google Scholar 

  49. T. Satoh and M. Hosokawa. The mammalian carboxylesterases: from molecules to functions. Ann. Rev. Pharmacol. Toxicol. 38:257-288 (1998).

    Google Scholar 

  50. B. Wittmann-Liebold, A. W. Geissler, A. Lin, and I. G. Wool. Sequence of the aminoterminal region of rat liver ribosomal proteins S4, S6, S8, L6, L7a, L18, L27, L30, L37, L37a, and L39. J. Supramol. Struct. 12:425-433 (1979).

    PubMed  Google Scholar 

  51. L. E. Panin, V. F. Maksimov, and I. M. Korostyshevskaia. Activation of nucleolar DNA and ribosome biosynthesis in hepatocytes under the effect of glucocorticoids and high density lipoproteins. Tsitologiia 42:461-467 (2000).

    PubMed  Google Scholar 

  52. E. Mezey and J. J. Potter. Rat liver alcohol dehydrogenase activity: effects of growth hormone and hypophysectomy. Endocrinology 104:1667-1673 (1979).

    PubMed  Google Scholar 

  53. E. Mezey, J. J. Potter, and D. L. Rhodes. Effect of growth hormone on alcohol dehydrogenase activity in hepatocyte culture. Hepatology 6:1386-1390 (1986).

    PubMed  Google Scholar 

  54. Y. N. Sun, D. C. DuBois, R. R. Almon, N. A. Pyszczynski, and W. J. Jusko. Dosedependence and repeated-dose studies for receptor_gene-mediated pharmacodynamics of methylprednisolone on glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver. J. Pharmacokin. Biopharm. 26:619-648 (1998).

    Google Scholar 

  55. S. Dernek, B. Tunerir, B. Sevin, R. Aslan, O. Uyguc, and T. Kural. The effects of methylprednisolone on complement, immunoglobulins and pulmonary neutrophil sequestration during cardiopulmonary bypass. Cardiovasc. Surg. 7:414-8 (1999).

    PubMed  Google Scholar 

  56. C. A. Baumann, M. Badamchian, and A. L. Goldstein. Thymosin alpha 1 antagonizes dexamethasone and CD3-induced apoptosis of CD4C CD8C thymocytes through the activation of cAMP and protein kinase C dependent second messenger pathways. Mech. Ageing Dev. 94:85-101 (1997).

    PubMed  Google Scholar 

  57. K. Okamoto and F. Isohashi. Purification and primary structure of a macromoleculartranslocation inhibitor II of glucocorticoid-receptor binding to nuclei from rat liver. Inhibitor II is the 11.5-kDa Zn2+-binding protein (parathymosin). Europ. J. Biochem. 267:155-162 (2000).

    PubMed  Google Scholar 

  58. Y. Calmus, C. Arvieux, P. Gane, E. Boucher, B. Nordlinger, P. Rouger, and R. Poupon. Cholestasis induces major histocompatibility complex class I expression in hepatocytes [see comments]. Gastroenterology 102:1371-1377 (1992).

    PubMed  Google Scholar 

  59. P. Nyberg, A. L. Wikman, I. Nennesmo, and I. Lundberg. Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis. J. Rheumatol. 27:940-948 (2000).

    PubMed  Google Scholar 

  60. F. Rodriguez, M. Redondo, M. L. Hortas-Nieto, T. Tellez-Santana, V. Perez-Valero, and F. Ruiz-Cabello. Downmodulation of HLA class I expression by dexamethasone in MCF-7 cell line. Revista Espanola de Fisiologia 53:355-360 (1997).

    PubMed  Google Scholar 

  61. N. Hirai, M. Shimizu, T. Morioka, Y. Hinoue, N. Tanaka, K. Kobayashi, N. Hattori, and T. Hashimoto. Activities of the interferon system in patients with HBsAg-positive chronic hepatitis B during short-term steroid withdrawal therapy. Liver 8:138-145 (1988).

    PubMed  Google Scholar 

  62. H. T. Maecker, S. C. Todd, and S. Levy. The tetraspanin superfamily: molecular facilitators. FASEB J. 11:428-442 (1997).

    PubMed  Google Scholar 

  63. P. Pileri, Y. Uematsu, S. Campagnoli, G. Galli, F. Falugi, R. Petracca, A. J. Weiner, M. Houghton, D. Rosa, G. Grandi, and S. Abrignani. Binding of hepatitis C virus to CD81. Science 282:938-941 (1998).

    PubMed  Google Scholar 

  64. V. Haridas, J. Ni, A. Meager, J. Su, G. L. Yu, Y. Zhai, H. Kyaw, K. T. Akama, J. Hu, L. J. Van Eldik, and B. B. Aggarwal. TRANK, a novel cytokine that activates NF-kappa B and c-Jun N-terminal kinase. J. Immunol. 161:1-6 (1998).

    PubMed  Google Scholar 

  65. D. Y. Jin, H. Z. Chae, S. G. Rhee, and K. T. Jeang. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J. Biol. Chem. 272:30952-30961 (1997).

    PubMed  Google Scholar 

  66. B. Hogemann, G. Edel, K. Schwarz, R. Krech, and H. Kresse. Expression of biglycan, decorin and proteoglycan-100_CSF-1 in normal and fibrotic human liver. Pathol. Res. Pract. 193:747-751 (1997).

    PubMed  Google Scholar 

  67. J. Huang, R. Olivenstein, R. Taha, Q. Hamid, and M. Ludwig. Enhanced proteoglycan deposition in the airway wall of atopic asthmatics. Am. J. Res. Crit. Care Med. 160:725-729 (1999).

    Google Scholar 

  68. E. Tufvesson, and G. Westergren-Thorsson. Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha. J. Cel. Biochem. 77:298-309 (2000).

    Google Scholar 

  69. H. E. Birch and G. Schreiber. Transcriptional regulation of plasma protein synthesis during inflammation. J. Biol. Chem. 261:8077-8080 (1986).

    PubMed  Google Scholar 

  70. G. Le Cam and A. Le Cam. Synthesis of the growth hormone-regulated rat liver antiprotease GHR-P63 is inhibited by acute inflammation. FEBS Letters 210:1-5 (1987).

    PubMed  Google Scholar 

  71. A. Le Cam, G. Pages, P. Auberger, G. Le Cam, P. Leopold, R. Benarous, and N. Glaichenhaus. Study of a growth hormone-regulated protein secreted by rat hepatocytes: Almon et al. 128:cDNA cloning, anti-protease activity and regulation of its synthesis by various hormones. EMBO J. 6:1225-1232 (1987).

    PubMed  Google Scholar 

  72. B. Dahlback. Blood coagulation. Lancet 355:1627-1632 (2000).

    PubMed  Google Scholar 

  73. G. Eggertsen, G. Hudson, B. Shiels, D. Reed, and G. H. Fey. Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor from the alpha-macroglobulin-complement family. Mol. Biol. Med. 8:287-302 (1991).

    PubMed  Google Scholar 

  74. J. P. Lebreton, M. Hiron, D. Biou, and M. Daveau. Regulation of alpha 1-acid glycoprotein plasma concentration by sex steroids and adrenal-cortical hormones during experimental inflammation in the rat. Inflammation 12:413-424 (1988).

    PubMed  Google Scholar 

  75. L. E. Jensen and A. S. Whitehead. Regulation of serum amyloid A protein expression during the acute-phase response. Biochem. J. 334:489-503 (1998).

    PubMed  Google Scholar 

  76. T. Egawa, H. Ito, H. Nakamura, H. Yamamoto, and S. Kishimoto. Hormonal regulation of vitamin D-binding protein production by a human hepatoma cell line. Biochem. Internat. 28:551-557 (1992).

    Google Scholar 

  77. R. H. van de Poel, J. C. Meijers, B. Dahlbreck, and B. N. Bouma. C4b-binding protein (C4BP) beta-chain Short Consensus Repeat-2 specifically contributes to the interaction of C4BP with protein S. Blood Cells, Mol. Dis. 25:279-286 (1999).

    Google Scholar 

  78. K. Kasutani, N. Itoh, M. Kanekiyo, N. Muto, and K. Tanaka. Requirement for cooperative interaction of interleukin-6 responsive element type 2 and glucocorticoid responsive element in the synergistic activation of mouse metallothionein-I gene by interleukin-6 and glucocorticoid. Toxicol. Appl. Pharmacol. 151:143-151 (1998).

    PubMed  Google Scholar 

  79. G. S. Marks, J. K. Stephens, P. Fischer, and R. Morgan. Hormonal effects on the regulation of hepatic heme biosynthesis. Mol. Cell. Biochem. 25:111-123 (1979).

    PubMed  Google Scholar 

  80. A. G. Goodridge. Dietary regulation of gene expression: enzymes involved in carbohydrate and lipid metabolism. Ann. Rev. Nutr. 7:157-185 (1987).

    Google Scholar 

  81. G. Fiermonte, V. Dolce, R. Arrigoni, M. J. Runswick, J. E. Walker, and F. Palmieri. Organization and sequence of the gene for the human mitochondrial dicarboxylate carrier: evolution of the carrier family. Biochem. J. 344:953-960 (1999).

    PubMed  Google Scholar 

  82. N. Begum, H. M. Tepperman, and J. Tepperman. Effect of dexamethasone on adipose tissue and liver pyruvate dehydrogenase and its stimulation by insulin-generated chemical mediator. Endocrinology 114:99-107 (1984).

    PubMed  Google Scholar 

  83. A. J. Barak, H. C. Beckenhauer, and D. J. Tuma. Betaine, ethanol, and the liver: a review. Alcohol 13:395-398 (1996).

    PubMed  Google Scholar 

  84. K. O, E. G. Lynn, Y. H. Chung, Y. L. Siow, R. Y. Man, and P. C. Choy. Homocysteine stimulates the production and secretion of cholesterol in hepatic cells. Biochim. Biophys. Acta 1393:317-324 (1998).

    PubMed  Google Scholar 

  85. M. Passreiter, M. Anton, D. Lay, R. Frank, C. Harter, F. T. Wieland, K. Gorgas, and W. W. Just. Peroxisome biogenesis: involvement of ARF and coatomer. J. Cell Biol. 141:373-383 (1998).

    PubMed  Google Scholar 

  86. G. W. Goodwin, P. M. Rougraff, E. J. Davis, and R. A. Harris. Purification and characterization of methylmalonate-semialdehyde dehydrogenase from rat liver. Identity to malonate-semialdehyde dehydrogenase. J. Biol. Chem. 264:14965-14971 (1989).

    PubMed  Google Scholar 

  87. Y. Kikuta, E. Kusunose, M. Ito, and M. Kusunose. Purification and characterization of recombinant rat hepatic CYP4F1. Arch. Biochem. Biophys. 369:193-196 (1999).

    PubMed  Google Scholar 

  88. G. Luo, D. C. Zeldin, J. A. Blaisdell, E. Hodgson, and J. A. Goldstein. Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acid. Arch. Biochem. Biophys. 357:45-57 (1998).

    PubMed  Google Scholar 

  89. K. Sogawa, O. Gotoh, K. Kawajiri, T. Harada, and Y. Fujii-Kuriyama. Complete nucleotide sequence of a methylcholanthrene-inducible cytochrome P-450 (P-450d) gene in the rat. J. Biol. Chem. 260:5026-5032 (1985).

    PubMed  Google Scholar 

  90. R. Reiter and A. Wendel. Selenium and drug metabolism-I. Multiple modulations of mouse liver enzymes. Biochem. Pharmacol. 32:3063-3067 (1983).

    PubMed  Google Scholar 

  91. P. A. Bell, C. N. Falany, P. McQuiddy, and C. B. Kasper. Glucocorticoid repression and basal regulation of the epoxide hydrolase promoter. Arch. Biochem. Biophys. 279:363-369 (1990).

    PubMed  Google Scholar 

  92. N. Ueda and S. Yamamoto. Anandamide amidohydrolase (fatty acid amide hydrolase). Prostaglandins & Other Lipid Mediators 61:19-28 (2000).

    Google Scholar 

  93. W. Zhu, L. Song, H. Zhang, L. Matoney, E. LeCluyse, and B. Yan. Dexamethasone differentially regulates expression of carboxylesterase genes in humans and rats. Drug Metab. Dis. 28:186-191 (2000).

    Google Scholar 

  94. J. Laborda. The role of the epidermal growth factor-like protein dlk in cell differentiation. Histol. Histopathol. 15:119-129 (2000).

    PubMed  Google Scholar 

  95. S. Weissbarth, H. Maker, I. Raes, T. Brannan, E. Laoin, and G. Lehrer. The activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in rat tissues. J. Neurochem. 37:677-680 (1981).

    PubMed  Google Scholar 

  96. R. Meyer and F. McMorris. Synergistic enzyme induction by glucocorticoids and cyclic AMP observed in gliomaBhepatoma cell hybrids but not in their parents. Som. Cell Mol. Gen. 10:15309 (1984).

    Google Scholar 

  97. D. C. Guttridge, A. L. Lau, and D. D. Cunningham. Protease nexin-1, a thrombin inhibitor, is regulated by interleukin-1 and dexamethasone in normal human fibroblasts. J. Biol. Chem. 268:18966-18974 (1993).

    PubMed  Google Scholar 

  98. D. W. Crabb, Studies on the hormonal regulation of rat liver alcohol dehydrogenase. Prog. Clin. Bio. Res. 232:245-258 (1987).

    Google Scholar 

  99. H. D. Gresham, I. L. Graham, G. L. Griffin, J. C. Hsieh, L. J. Dong, A. E. Chung, and R. M. Senior. Domain-specific interactions between entactin and neutrophil integrins. G2 domain ligation of integrin alpha3beta1 and E domain ligation of the leukocyte response integrin signal for different responses. J. Biol. Chem. 271:30587-30594 (1996).

    PubMed  Google Scholar 

  100. S. Schwoegler, K. Neubauer, T. Knittel, A. E. Chung, and G. Ramadori. Entactin gene expression in normal and fibrotic rat liver and in rat liver cells. Lab. Inves. 70:525-36 (1994).

    Google Scholar 

  101. Q. Liu, Y. Feng, and M. Forgac. Activity and in vitro reassembly of the coated vesicle (HC)-ATPase requires the 50-kDa subunit of the clathrin assembly complex AP-2. J. Biol. Chem. 269:31592-31597 (1994).

    PubMed  Google Scholar 

  102. Y. Zhang and J. P. Allison. Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. Proc. Nat. Acad. Sci. U.S.A. 94:9273-9278 (1997).

    Google Scholar 

  103. A. Pol, D. Ortega, and C. Enrich. Identification of cytoskeleton-associated proteins in isolated rat liver endosomes. Biochem. J. 327:741-746 (1997).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, 14260, USA

    Richard R. Almon & Debra C. DuBois

  2. Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14260, USA

    Richard R. Almon, Debra C. DuBois, Emily H. Brandenburg, Wei Shi, Shuzhong Zhang, Robert M. Straubinger & William J. Jusko

Authors
  1. Richard R. Almon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Debra C. DuBois
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily H. Brandenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuzhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert M. Straubinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. William J. Jusko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard R. Almon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Almon, R.R., DuBois, D.C., Brandenburg, E.H. et al. Pharmacodynamics and Pharmacogenomics of Diverse Receptor-Mediated Effects of Methylprednisolone in Rats Using Microarray Analysis. J Pharmacokinet Pharmacodyn 29, 103–129 (2002). https://doi.org/10.1023/A:1019762323576

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1019762323576

Search

Navigation