Expression and functional activity of P-glycoprotein in subcellular compartments of cultured brain cells.
Published: 2007
Language: eng
Number of pages: 127
ISBN-13: 9780494273883
Description: P-glycoprotein is a plasma membrane drug efflux protein implicated in extrusion of therapeutic compounds out of a cell. This study investigated the localization, expression and activity of P-glycoprotein at the nuclear envelope of rat brain microvessel endothelial (RBE4) and microglial (MLS-9) cell lines. Immunogold and fluorescent cytochemical studies using P-glycoprotein monoclonal antibodies C219 and/or MRK16 demonstrated the localization of the protein at the nucleus of RBE4 and MLS-9 cells. Immunoblot analysis also detected a band of &sim;170 kDa in crude nuclear membranes prepared from isolated nuclei of RBE4 and MLS-9 cells. Fluorescent microscopy studies demonstrated an increase in doxorubicin, a known P-glycoprotein substrate, accumulation in the nucleus in the presence of P-glycoprotein inhibitors, suggesting that the subcellular glycoprotein may possess activity. Subcellular activity of P-glycoprotein at the nuclear envelope may be involved in efflux of therapeutic compounds out of the nucleus of brain cells and may contribute to multidrug resistance.
Notes: Source: Masters Abstracts International, Volume: 45-06, page: 3141.

Thesis (M.Sc.)--University of Toronto, 2007.

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