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Pathway Description
Prednisolone Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Prednisolone is a synthetic glucocorticoid that is used clinically for its anti-inflammatory properties. Prednisolone diffuses passively across the cell membrane, where it binds to glucocorticoid receptors in the cytoplasm. Upon binding, the glucocorticoid receptor (GR) dissociates from heat shock protein 90, and translocate into the nucleus. In the nucleus, GR dimers can bind to glucocorticoid response element (GRE) in the promoter region of anti-inflammatory genes, which activates their transcription. GRs also inhibit transcription of inflammatory mediators by binding to negative GRE (nGRE). GRs further interact with the transcription factors cAMP-responsive element binding protein and NF-kappa-B, and inihibit their activation of inflammatory gene transcription. GRs also recruit histone deacetylase 2 to inflammatory gene loci on DNA, which leads to DNA condensation and suppression of gene expression.
References
Prednisolone Pathway References
Barnes PJ, Adcock IM: Glucocorticoid resistance in inflammatory diseases. Lancet. 2009 May 30;373(9678):1905-17. doi: 10.1016/S0140-6736(09)60326-3.
Pubmed: 19482216
Frey BM, Frey FJ: Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet. 1990 Aug;19(2):126-46. doi: 10.2165/00003088-199019020-00003.
Pubmed: 2199128
Pujolsa L, Mullol J, Picado C: Glucocorticoid receptor in human respiratory epithelial cells. Neuroimmunomodulation. 2009;16(5):290-9. doi: 10.1159/000216187. Epub 2009 Jun 29.
Pubmed: 19571590
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