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ABCC1 is related to the protection of the distal nephron against hyperosmolality and high sodium environment: possible implications for cancer chemotherapy

Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find...

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Published in:PloS one 2013-06, Vol.8 (6), p.e68049-e68049
Main Authors: Fonseca, Leonardo M, Alvarez, Adriana B, Rodrigues, Rachel C, Santos, Diego H F, Lopes, Anibal G, Capella, Marcia A M
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cited_by cdi_FETCH-LOGICAL-c526t-bd03701f4dc0bab46e04dd40e52ea7bf0a83af69ba0efc248eb9fdc55e98a2003
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creator Fonseca, Leonardo M
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description Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find out whether ABCC1 has a role in protecting cells from the distal nephron against the stress caused by high medullar osmolality. MA104 cells were treated with high concentrations of sodium chloride, urea, or both to raise the osmolality of the culture medium. Cell viability was accessed by MTT and trypan blue assays. ABCC1 expression and extrusion of carboxi-fluorescein (CF), a fluorescent ABCC1 substrate, were measured by flow cytometry. Incubation of MA104 cells in a high sodium concentration medium resulted in changes in cell granularity and altered expression and activity of ABCC1. Urea did not alter ABCC1 expression or activity, but reversed the observed NaCl effects. High sodium concentrations also had a negative effect on cell viability and urea also protected cells against this effect. Our findings demonstrate that ABCC1 plays a significant role in the protection of kidney epithelial cells against the stress caused by high sodium environment present in renal medulla.
doi_str_mv 10.1371/journal.pone.0068049
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subjects ABCC1 protein
Animals
Bile
Biological Transport - physiology
Biology
Cancer
Cancer therapies
Cell culture
Cell Survival - physiology
Cells, Cultured
Chemotherapy
Chlorine compounds
Cytometry
Dogs
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - physiology
Extrusion
Flow cytometry
Fluorescein
Fluorescence
Glutathione
Glutathione - metabolism
Haplorhini
Incubation
Kidney Medulla - metabolism
Kidney Medulla - physiology
Kidneys
Madin Darby Canine Kidney Cells
Medicine
Multidrug resistance
Multidrug Resistance-Associated Proteins - metabolism
Neoplasms - metabolism
Neoplasms - physiopathology
Nephrons - metabolism
Nephrons - physiology
Osmolar Concentration
Osmotic pressure
Oxidative stress
Physiology
Protein transport
Proteins
Rodents
Sodium
Sodium chloride
Sodium Chloride - metabolism
Substrates
Swine
Toxicology
Urea
title ABCC1 is related to the protection of the distal nephron against hyperosmolality and high sodium environment: possible implications for cancer chemotherapy
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