| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, University Health Science Center, San Antonio, Texas 78229-3900
Renal A6 epithelial cells were used to
determine the mechanism by which protein kinase C (PKC) decreases
epithelial Na+ channel (ENaC) activity. Activation of PKC
reduced relative Na+ reabsorption to <20% within 60 min.
This decrease was sustained over the next 24-48 h. In response to
PKC signaling, 
-, 
-, and 
-ENaC levels were 0.97, 0.36, and
0.39, respectively, after 24 h, with the levels of the latter two
subunits being significantly decreased. The PKC-mediated decreases in
- and -ENaC were significantly reversed by simultaneous addition
of the mitogen-activated protein kinase (MAPK)/extracellular
signal-regulated kinase-1/2 inhibitors U-0126 and PD-98059. These
inhibitors, in addition, protected Na+ reabsorption from
PKC, demonstrating that the MAPK1/2 cascade, in some instances, plays a
central role in downregulation of ENaC activity. The effects of PKC on
- and -ENaC levels were additive with those of inhibitors of
transcription (actinomycin D) and translation (emetine and
cycloheximide), suggesting that PKC promotes subunit degradation and
does not affect subunit synthesis. The bulk of whole cell -ENaC was
degraded within 1 h after treatment with inhibitors of synthesis;
however, a significant pool was "protected" from inhibitors for up
to 12 h. PKC affected this protected pool of -ENaC. Moreover,
proteosome inhibitors (MG-132 and lactacystin) reversed PKC effects on
this protected pool of -ENaC. Thus PKC signaling via MAPK1/2 cascade
activation in A6 cells promotes degradation of -ENaC.
proteosome; hypertension; sodium transport; MG-132; MG-262; lactacystin
This article has been cited by other articles:
|
|
 |
|
  V. Bhalla and K. R. Hallows Mechanisms of ENaC Regulation and Clinical Implications J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1845 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bugaj, O. Pochynyuk, E. Mironova, A. Vandewalle, J. L. Medina, and J. D. Stockand Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1063 - F1070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Pochynyuk, V. Bugaj, A. Vandewalle, and J. D. Stockand Purinergic control of apical plasma membrane PI(4,5)P2 levels sets ENaC activity in principal cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F38 - F46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, and J. D. Stockand Molecular Determinants of PI(4,5)P2 and PI(3,4,5)P3 Regulation of the Epithelial Na+ Channel J. Gen. Physiol., September 24, 2007; 130(4): 399 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Falin and C. U. Cotton Acute Downregulation of ENaC by EGF Involves the PY Motif and Putative ERK Phosphorylation Site J. Gen. Physiol., August 27, 2007; 130(3): 313 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Good Nongenomic Actions of Aldosterone on the Renal Tubule Hypertension, April 1, 2007; 49(4): 728 - 739. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bhalla, N. M. Oyster, A. C. Fitch, M. A. Wijngaarden, D. Neumann, U. Schlattner, D. Pearce, and K. R. Hallows AMP-activated Kinase Inhibits the Epithelial Na+ Channel through Functional Regulation of the Ubiquitin Ligase Nedd4-2 J. Biol. Chem., September 8, 2006; 281(36): 26159 - 26169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Yan, L. Suaud, T. R. Kleyman, and R. C. Rubenstein Differential modulation of a polymorphism in the COOH terminus of the {alpha}-subunit of the human epithelial sodium channel by protein kinase C{delta} Am J Physiol Renal Physiol, February 1, 2006; 290(2): F279 - F288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Markadieu, R. Crutzen, D. Blero, C. Erneux, and R. Beauwens Hydrogen peroxide and epidermal growth factor activate phosphatidylinositol 3-kinase and increase sodium transport in A6 cell monolayers Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1201 - F1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Falin, I. E. Veizis, and C. U. Cotton A role for ERK1/2 in EGF- and ATP-dependent regulation of amiloride-sensitive sodium absorption Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1003 - C1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Hanai, T. Mammoto, P. Seth, K. Mori, S. A. Karumanchi, J. Barasch, and V. P. Sukhatme Lipocalin 2 Diminishes Invasiveness and Metastasis of Ras-transformed Cells J. Biol. Chem., April 8, 2005; 280(14): 13641 - 13647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tong and J. D. Stockand Receptor tyrosine kinases mediate epithelial Na+ channel inhibition by epidermal growth factor Am J Physiol Renal Physiol, January 1, 2005; 288(1): F150 - F161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Awayda, A. Bengrine, N. A. Tobey, J. D. Stockand, and R. C. Orlando Nonselective cation transport in native esophageal epithelia Am J Physiol Cell Physiol, August 1, 2004; 287(2): C395 - C402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Grossmann, R. Freudinger, S. Mildenberger, A. W. Krug, and M. Gekle Evidence for epidermal growth factor receptor as negative-feedback control in aldosterone-induced Na+ reabsorption Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1226 - F1231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tong, R. E. Booth, R. T. Worrell, and J. D. Stockand Regulation of Na+ transport by aldosterone: signaling convergence and cross talk between the PI3-K and MAPK1/2 cascades Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1232 - F1238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Weisz and J. P. Johnson Noncoordinate regulation of ENaC: paradigm lost? Am J Physiol Renal Physiol, November 1, 2003; 285(5): F833 - F842. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
