NDLI: K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

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K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, Yan Lin, Dao-Hong Wang, Zhi-Jian Jin, Yan Yang, Baofeng Wang, Wen-Hui
Description	Country affiliation: China Author Affiliation: Zhang Y ( Department of Pharmacology, Harbin Medical University, Harbin, China.)
Abstract	We used Western blot analysis to examine the effect of dietary K intake on the expression of serine/threonine protein phosphatase in the kidney. K restriction significantly decreased the expression of catalytic subunit of protein phosphatase (PP)2B but increased the expression of PP2B regulatory subunit in both rat and mouse kidney. However, K depletion did not affect the expression of PP1 and PP2A. Treatment of M-1 cells, mouse cortical collecting duct (CCD) cells, or 293T cells with glucose oxidase (GO), which generates superoxide anions through glucose metabolism, mimicked the effect of K restriction on PP2B expression and significantly decreased expression of PP2B catalytic subunits. However, GO treatment increased expression of regulatory subunit of PP2B and had no effect on expression of PP1, PP2A, and protein tyrosine phosphatase 1D. Moreover, deletion of gp91-containing NADPH oxidase abolished the effect of K depletion on PP2B. Thus superoxide anions or related products may mediate the inhibitory effect of K restriction on the expression of PP2B catalytic subunit. We also used patch-clamp technique to study the effect of inhibiting PP2B on renal outer medullary K (ROMK) channels in the CCD. Application of cyclosporin A or FK506, inhibitors of PP2B, significantly decreased ROMK channels, and the effect of PP2B inhibitors was abolished by blocking p38 mitogen-activated protein kinase (MAPK) and ERK. Furthermore, Western blot demonstrated that inhibition of PP2B with cyclosporin A or small interfering RNA increased the phosphorylation of ERK and p38 MAPK. We conclude that K restriction suppresses the expression of PP2B catalytic subunits and that inhibition of PP2B decreases ROMK channel activity through stimulation of MAPK in the CCD.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
DOI	10.1152/ajpcell.00528.2007
Journal	American Journal of Physiology - Cell Physiology
Issue Number	3
Volume Number	294
Language	English
Publisher	American Physiological Society
Publisher Date	2008-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Calcineurin Metabolism Kidney Tubules, Collecting Potassium Channels, Inwardly Rectifying Potassium, Dietary Signal Transduction Animals Blotting, Western Genetics Calcineurin Inhibitors Catalytic Domain Cell Line Cyclosporine Pharmacology Down-regulation Enzyme Inhibitors Extracellular Signal-regulated Map Kinases Glucose Oxidase Drug Effects Enzymology Membrane Glycoproteins Membrane Potentials Mice Mice, Inbred C57bl Mice, Knockout Nadph Oxidase Patch-clamp Techniques Phosphorylation Administration & Dosage Protein Phosphatase 1 Protein Phosphatase 2 Rna Interference Rna, Small Interfering Rats, Sprague-dawley Superoxides Tacrolimus P38 Mitogen-activated Protein Kinases Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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Mitogen-Activated Protein Kinases Inhibit the ROMK (Kir 1.1)-Like Small Conductance K Channels in the Cortical Collecting Duct

Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.

K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

Role of gp91phox -containing NADPH oxidase in mediating the effect of K restriction on ROMK channels and renal K excretion.

Regulation of potassium (K) handling in the renal collecting duct.

Inhibition of phosphatidylinositol 3-kinase stimulates activity of the small-conductance K channel in the CCD

Effect of hydrogen peroxide on ROMK channels in the cortical collecting duct

Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects.

Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney

K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

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Mitogen-Activated Protein Kinases Inhibit the ROMK (Kir 1.1)-Like Small Conductance K Channels in the Cortical Collecting Duct

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