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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068049

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.