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Role of breast cancer resistance protein in obesity associated chronic low grade inflammation
Author(s) -
Mishra Jayshree,
Kumar Narendra
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1062.8
Subject(s) - abcg2 , pharmacology , inflammation , transporter , drug , drug metabolism , medicine , in vivo , atp binding cassette transporter , cancer , efflux , biology , biochemistry , microbiology and biotechnology , gene
Objective The major immunological manifestation in diabetes/obesity is characterized by chronic low grade inflammation that leads to altered drug metabolism and disposition. Alteration in drug metabolism has profound impact on the pharmacotherapy of widely used clinically relevant medications in terms of safety and efficacy and increased toxicity. Altered drug metabolism and disposition is associated with the alteration in the expression and activity of the several key drug metabolizing enzymes (DMEs) and transporters. However, the role of inflammation in regulation of drug transporters in diabetes/obesity remains unclear. Breast cancer resistance protein (BCRP) is a principal drug transporter protein expressed in intestine, liver and brain extrudes a broad range of xenochemicals and to protect the organism against xenotoxicity by facilitating excretion, and limiting absorption of potentially toxic substrate molecules, including many chemotherapeutic drugs, the possible involvement of BCRP in obesity is poorly understood. It is critical to understand the mechanisms that regulate mucosal detoxification mediated by BCRP under normal physiological conditions and under the chronic low grade inflammation as seen in obesity. A better understanding of the mechanistic details underlying the regulation of BCRP in obesity will contribute towards development of powerful in vitro and in vivo tools in predicting the drug response and opt for better drug design and development. Materials and Methods Freshly dissected human colon tissue from normal and obese were immunostained and analyzed for BCRP (Novus). Phosphorylation status of this protein in both normal and obese were assessed through immunoprecipitation. Functional activity of BCRP was measured using Efflux id Gold kits from Enzo Life sciences. Summary of Results Our results show that colonic epithelial cells of normal subject express BCRP, however there is a substantial decrease in expression of BCRP in obese patients. Also in obese patients there is a substantial decreases in the tyrosine phosphorylation status of BCRP. Expression and activity of BCRP was found to be significantly reduced in the induced with high fat diet. Conclusion Our data suggest that colonic BCRP plays an important role in obesity. Further, our goal is to facilitate a better understanding of the mechanistic role of BCRP in the process of chronic low grade inflammation and associated chronic diseases. Support or Funding Information Health‐ SBIR (GM109528)