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Peroxisome proliferator activated receptor – alpha regulation of sodium transport mechanisms in human primary renal proximal tubule epithelial cells during acute Angiotensin II treatment
Author(s) -
Doh Kwame,
Hudson Tamaro,
Lee Dexter L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1115.17
Subject(s) - sodium–hydrogen antiporter , fenofibrate , reabsorption , endocrinology , chemistry , angiotensin ii , renal sodium reabsorption , medicine , kidney , receptor , peroxisome proliferator activated receptor , renin–angiotensin system , sodium , biology , biochemistry , organic chemistry , blood pressure
Angiotensin II (Ang II) is important for Na + regulation in the kidney. Proteins in the proximal tubule (PT) epithelial cells such as the sodium hydrogen exchanger (NHE3), sodium hydrogen exchanger regulatory factor‐1 (NHERF‐1), Na + /K + ATPase, NaPi2 serve as Na + transporters. Studies have demonstrated that NHERF‐1 interacts with NaPi2 and NHE3 to regulate Na + transport. Peroxisome proliferator activated receptor‐alpha (PPAR‐α) activation reduces Na + /K + ATPase activity but is important for its expression. This study tests the hypothesis that PPAR‐α activation stimulates NHERF‐1 to interact with NHE3, NaPi2 and Na + /K + ATPase to reduce Na + reabsorption in PT cells during Ang II stimulation. Human primary renal proximal tubule epithelial cells (PREC) were used during passage 4 and plated at a density of 2 × 10 6 /dish. PRECs were treated for 20 hours as follows: control plates, Ang II (10 −9 M), fenofibrate (a PPAR‐α agonist)( 10 −7 M) and Ang II + fenofibrate. Western blots were performed to determine the expression (optical density/area) of NHERF‐1, NHE3, Na + /K + ATPase and NaPi2 in PRECs. Fenofibrate, Ang II and Ang II + Fenofibrate significantly increased NHERF‐1 expression in PRECs above control. We did not observe differences in NaPi2 or Na + /K + ATPase expression between the groups. Our results suggest fenofibrate regulates Na + reabsorption in PRECs by increasing NHERF‐1 expression. Our results also indicate that a low dose of Ang II directly stimulates NHERF‐1 expression in PRECs. Future studies are needed to determine the dose dependent effect of Ang II and fenofibrate on NaPi2, Na + /K + ATPase, NHE3 expression and activity. Support: 5K01HL092593–05