Abstract
AimsGlutathione (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.Main MethodsMA104 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.Key FindingsIncubation 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.SignificanceOur 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.
Highlights
Multidrug resistance (MDR) is still the main cause of failure in cancer chemotherapy
MDR is multifactorial, it is primarily characterized by an ATP-dependent reduction in intracellular drug accumulation, due to the overexpression of three proteins belonging to the ABC transporters super family: Pglycoprotein (ABCB1), breast cancer protein (BCRP or ABCG2) or multidrug resistance-associated protein 1 (MRP1 or ABCC1)
We have previously shown that antibodies against human ABCB1 and ABCC1 labeled this cell line [28,29]
Summary
Multidrug resistance (MDR) is still the main cause of failure in cancer chemotherapy. ABCC1, previously known as MRP1, is a transmembrane protein originally recognized as a transporter related to multidrug resistance phenotype in some cancer cells [3,4,5,6] but subsequent studies showed that this protein is ubiquitously expressed in virtually all organs in mammals, including humans [7,8]. This transporter has a great importance in inflammatory processes and oxidative injury, given that it transports both reduced and oxidized glutathione, leukotriene C4 and prostaglandins [7,9]. Its physiological role has been studied in several organs and systems and one of the most important discoveries is the fact that its presence is essential for the hypertensive response to angiotensin II [10]
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