Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway
| Autor: | Boyu Tan, Lei Zhang, Mingming Li, Hongyan Wei, Feng Xu, Zhijun Xiao, Ting Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty glucocorticoid and adrenergic signaling pathway Pharmacology drug-metabolizing enzymes (DMEs) Cell Line 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Piperidines Internal medicine medicine chronic unpredicted mild stress(CUMS) Animals Gene Regulatory Networks Glucocorticoids Dexamethasone Constitutive Androstane Receptor Pregnane X receptor repaglinide business.industry Depression Gene Expression Profiling Repaglinide Biosynthetic Pathways Rats Disease Models Animal 030104 developmental biology Endocrinology Epinephrine Oncology Gene Expression Regulation Liver Pharmacogenetics Carbamates Signal transduction business 030217 neurology & neurosurgery Glucocorticoid Drug metabolism Stress Psychological medicine.drug Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Hongyan Wei 1, 2, * , Ting Zhou 1, * , Boyu Tan 2 , Lei Zhang 3 , Mingming Li 1 , Zhijun Xiao 1 and Feng Xu 1, 3 1 Fengxian Hospital, Southern Medical University, Shanghai, China 2 Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, China 3 Joint Research Center for Translation Medicine, East China Normal University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Feng Xu, email: andrewfxu1998@gmail.com Keywords: chronic unpredicted mild stress(CUMS), depression, repaglinide, drug-metabolizing enzymes (DMEs), glucocorticoid and adrenergic signaling pathway Received: March 29, 2017 Accepted: April 24, 2017 Published: May 15, 2017 ABSTRACT Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats. |
| Databáze: | OpenAIRE |
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