PMID- 18202152
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20211020
IS  - 0888-8809 (Print)
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Linking)
VI  - 22
IP  - 4
DP  - 2008 Apr
TI  - Aldosterone regulates rapid trafficking of epithelial sodium channel subunits in 
      renal cortical collecting duct cells via protein kinase D activation.
PG  - 881-92
LID - 10.1210/me.2007-0225 [doi]
AB  - Aldosterone elicits rapid physiological responses in target tissues such as the 
      distal nephron through the stimulation of cell signaling cascades. We identified 
      protein kinase D (PKD1) as an early signaling response to aldosterone treatment 
      in the M1-cortical collecting duct (M1-CCD) cell line. PKD1 activation was 
      blocked by the PKC inhibitor chelerythrine chloride and by rottlerin, a specific 
      inhibitor of PKCdelta. The activation of PKCdelta and PKCepsilon coincided with 
      PKD1 activation and while a complex was formed between PKD1 and PKCepsilon after 
      aldosterone treatment, there was a concurrent reduction in PKD1 association with 
      PKCdelta. A stable PKD1 knockdown M1-CCD-derrived clone was developed in which 
      PKD1 expression was 90% suppressed by gene silencing with a PKD1-specific siRNA. 
      The effect of aldosterone treatment on the subcellular distribution of enhanced 
      cyan fluorescent protein (eCFP)-tagged epithelial sodium channel (ENaC) subunits 
      in wild type (WT) and PKD1 suppressed cells was examined using confocal 
      microscopy. In an untreated confluent monolayer of M1-CCD cells, alpha, beta, and 
      gamma ENaC subunits were evenly distributed throughout the cytoplasm of WT and 
      PKD1-suppressed cells. After 2 min treatment, aldosterone stimulated the 
      localization of each of the ENaC subunits to discrete regions within the 
      cytoplasm of WT cells. The translocation of eCFP-ENaC subunits in WT cells was 
      inhibited by rottlerin and the mineralocorticoid receptor (MR) antagonist 
      spironolactone. No subcellular translocation of eCFP-ENaC subunits was observed 
      in PKD1-suppressed cells treated with aldosterone. These data demonstrate the 
      involvement of a novel MR/PKCdelta /PKD1 signaling cascade in the earliest ENaC 
      subunit intracellular trafficking events that follow aldosterone treatment.
FAU - McEneaney, Victoria
AU  - McEneaney V
AD  - Department of Molecular Medicine, Royal College of Surgeons in Ireland Education 
      and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
FAU - Harvey, Brian J
AU  - Harvey BJ
FAU - Thomas, Warren
AU  - Thomas W
LA  - eng
GR  - 060809/z/00/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080117
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Acetophenones)
RN  - 0 (Benzophenanthridines)
RN  - 0 (Benzopyrans)
RN  - 0 (Epithelial Sodium Channels)
RN  - 27O7W4T232 (Spironolactone)
RN  - 4964P6T9RB (Aldosterone)
RN  - E29LP3ZMUH (rottlerin)
RN  - E3B045W6X0 (chelerythrine)
RN  - EC 2.7.10.- (protein kinase D)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Aldosterone/*pharmacology
MH  - Animals
MH  - Benzophenanthridines/pharmacology
MH  - Benzopyrans/pharmacology
MH  - Biological Transport/drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme Activation/drug effects
MH  - Epithelial Sodium Channels/genetics/*metabolism
MH  - Immunoprecipitation
MH  - Kidney Cortex/cytology/drug effects/metabolism
MH  - Kidney Tubules, Collecting/cytology/*drug effects/metabolism
MH  - Mice
MH  - Microscopy, Confocal
MH  - Protein Kinase C/genetics/*metabolism
MH  - RNA Interference
MH  - Spironolactone/pharmacology
PMC - PMC5419554
EDAT- 2008/01/19 09:00
MHDA- 2008/07/22 09:00
PMCR- 2009/04/01
CRDT- 2008/01/19 09:00
PHST- 2008/01/19 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/01/19 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - me.2007-0225 [pii]
AID - 10.1210/me.2007-0225 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2008 Apr;22(4):881-92. doi: 10.1210/me.2007-0225. Epub 2008 Jan 
      17.