ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy

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.

Resistance to paclitaxel induces glycophenotype changes and mesenchymal-to-epithelial transition activation in the human prostate cancer cell line PC-3

“…32 Plates used for antibody labeling were blocked with BFS solution as processed as described in a previous work. 31 All flow cytometry analyses were performed using Summit Software.…”

“…All antibodies used in this study were acquired from Santa Cruz Biotechnology. 31 For the immunofluorescence assay, the parental and resistant cell lines were seeded onto round glass microscope coverslips inside 24 well plates at a 1 3 10 5 cell/well density. After 24 h of incubation, cells were fixed in a 4% para-formaldehyde solution during 15 min at 4°C and then washed with saline phosphate buffer (PBS pH 7.4).…”

Transcriptome analysis identifies activated signaling pathways and regulated ABC transporters and solute carriers after hyperosmotic stress in renal MDCK I cells

“…In the "Database of Osmoregulated Proteins in Mammalian Cells" only five ABC transporters have been registered as being affected by hyperosmolality: ABCC2, ABCC5, ABCD1, ABCD3 and ABCC7 [33]. To our knowledge two studies have investigated the link between hyperosmolality and ABC transporter expression [34,35]. In these studies, it was reported that ABCB1 (MDR1) and ABCC1 (MRP1) were up-regulated under hyperosmotic conditions.…”