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Expression and function of P-glycoprotein in human mesangial cells
1Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
The American Journal of Physiology
|November 1, 1994
Summary
Human mesangial cells express P-glycoprotein (PGP), a protein linked to multidrug resistance (MDR). PGP function in these cells can be inhibited, potentially impacting drug efficacy and cellular damage.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- P-glycoprotein (PGP) mediates multidrug resistance (MDR) in cancer cells.
- PGP is normally expressed in kidney proximal tubules and mesangium.
Purpose of the Study:
- To investigate PGP expression and function in human mesangial cell cultures.
- To assess the impact of PGP substrates on mesangial cell viability.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) for MDR1 gene expression.
- Immunodetection of PGP using MRK16 monoclonal antibody.
- Rhodamine-123 (R123) efflux assay to assess PGP function.
Main Results:
- Human mesangial cells express functional PGP, demonstrated by R123 efflux.
- R123 efflux was inhibited by cyclosporin A, verapamil, and vinblastine.
- PGP inhibition augmented Adriamycin cytotoxicity, reducing the 50% maximal growth-inhibitory dose.
Conclusions:
- Human mesangial cells express MDR1 and exhibit xenobiotic transport inhibitable by known PGP substrates.
- Exposure to PGP-transported drugs can lead to intracellular accumulation of toxic substrates.
- This accumulation ultimately damages mesangial cells, suggesting a role in kidney drug toxicity.