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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

AIMS: 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...

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Autores principales: Fonseca, Leonardo M., Alvarez, Adriana B., Rodrigues, Rachel C., Santos, Diego H. F., Lopes, Anibal G., Capella, Marcia A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695945/
https://www.ncbi.nlm.nih.gov/pubmed/23840808
http://dx.doi.org/10.1371/journal.pone.0068049
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author Fonseca, Leonardo M.
Alvarez, Adriana B.
Rodrigues, Rachel C.
Santos, Diego H. F.
Lopes, Anibal G.
Capella, Marcia A. M.
author_facet Fonseca, Leonardo M.
Alvarez, Adriana B.
Rodrigues, Rachel C.
Santos, Diego H. F.
Lopes, Anibal G.
Capella, Marcia A. M.
author_sort Fonseca, Leonardo M.
collection PubMed
description AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
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spelling pubmed-36959452013-07-09 ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy Fonseca, Leonardo M. Alvarez, Adriana B. Rodrigues, Rachel C. Santos, Diego H. F. Lopes, Anibal G. Capella, Marcia A. M. PLoS One Research Article AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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. Public Library of Science 2013-06-28 /pmc/articles/PMC3695945/ /pubmed/23840808 http://dx.doi.org/10.1371/journal.pone.0068049 Text en © 2013 Fonseca et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fonseca, Leonardo M.
Alvarez, Adriana B.
Rodrigues, Rachel C.
Santos, Diego H. F.
Lopes, Anibal G.
Capella, Marcia A. M.
ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title_full ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title_fullStr ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title_full_unstemmed ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title_short ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy
title_sort abcc1 is related to the protection of the distal nephron against hyperosmolality and high sodium environment: possible implications for cancer chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695945/
https://www.ncbi.nlm.nih.gov/pubmed/23840808
http://dx.doi.org/10.1371/journal.pone.0068049
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