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  1. Protein kinase D2 regulates epithelial sodium channel activity and aldosterone non-genomic responses in renal cortical collecting duct cells
    Thomas W, Dooley R, Quinn S, Robles MY, Harvey BJ
    Steroids, 2020 03;155:108553.
    PMID: 31836481 DOI: 10.1016/j.steroids.2019.108553
    Protein kinase D2 (PKD2) is a serine/threonine protein kinase which plays an important role in vesicle fission at the trans-Golgi network (TGN) to coordinate subcellular trafficking with gene expression. We found that in the rat kidney, PKD2 is specifically expressed in collecting duct principal cells predominantly at the apical membrane and with lower basal expression in cytosolic compartments. When rats were maintained on a Na+ depleted diet (<0.87 mmol Na+/kg) to increase plasma aldosterone levels, PKD2 became internalized to a cytoplasmic compartment. Treatment of murine M1 cortical collecting duct (M1-CCD) cells with aldosterone (10 nM) promoted PKD2 co-localization with the trans-Golgi network within 30 min. PKD2 underwent autophosphorylation at Ser876 within 10 min of aldosterone treatment and remained phosphorylated (active) for at least 24 h. A stable PKD2 shRNA knock-down (PKD2 KD) M1-CCD cell line was developed to study the role of PKD2 in epithelial Na+ channel (ENaC) trafficking and transepithelial Na+ transport (SCC) in epithelial monolayers grown in Ussing chambers. The PKD2 KD cells developed transepithelial resistance with kinetics equivalent to wild-type cells, however the transepithelial voltage and Na+ current were significantly elevated in PKD2 knock-down CCD epithelia. The higher basal SCC was due to increased ENaC activity. Aldosterone treatment for 24 h resulted in a decline in ENaC activity in the PKD2 KD cells as opposed to the increase observed in the wild-type cells. The paradoxical inhibition of SCC by aldosterone in PKD2 KD epithelium was attributed to a reduction in ENaC current and lower membrane abundance of ENaC, demonstrating that PKD2 plays a critical tonic role in ENaC trafficking and channel subunit stability. The rapid activation of PKD2 by aldosterone is synergistic with the transcriptional activity of MR and contributes to increased ENaC activity.
    Matched MeSH terms: Kidney Tubules, Collecting/metabolism
  2. Effects of testosterone on mean arterial pressure and aquaporin (AQP)-1, 2, 3, 4, 6 and 7 expressions in the kidney of orchidectomized, adult male Sprague-Dawley rats
    Loh SY, Giribabu N, Gholami K, Salleh N
    Arch Biochem Biophys, 2017 Jan 15;614:41-49.
    PMID: 28024836 DOI: 10.1016/j.abb.2016.12.008
    We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys.

    METHODS: Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 μg/kg/day or 250 μg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence.

    RESULTS: Testosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p 

    Matched MeSH terms: Kidney Tubules, Collecting/metabolism*
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