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J Physiol Sci
2014 Nov 01;646:433-43. doi: 10.1007/s12576-014-0338-3.
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Insulin is involved in transcriptional regulation of NKCC and the CFTR Cl(-) channel through PI3K activation and ERK inactivation in renal epithelial cells.
Sun H
,
Niisato N
,
Inui T
,
Marunaka Y
.
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It is is well known that insulin stimulates glucose transport and epithelial Na(+) channel (ENaC)-mediated Na(+) reabsorption; however, the action of insulin on Cl(-) secretion is not fully understood. In this study, we investigated the action of insulin on Na(+)-K(+)-2Cl(-) cotransporter (NKCC)-mediated Cl(-) secretion in epithelial A6 cells. Interestingly, insulin treatment remarkably enhanced the forskolin-stimulated Cl(-) secretion associated with an increase in apical Cl(-) conductance by upregulating mRNA expression of both CFTR and NKCC, although insulin treatment alone had no effect on the basal Cl(-) secretion or apical Cl(-) conductance without forskolin application. We next elucidated a role of phosphoinositide 3-kinase (PI3K) in the insulin-induced enhancement of the Cl(-) secretion, since insulin actually activated PI3K, resulting in activation of Akt, a downstream molecule of PI3K. LY294002 (a PI3K inhibitor) reduced the Cl(-) secretion by suppressing mRNA expression of NKCC, whereas insulin still had a stimulatory action on mRNA expression of CFTR even in the presence of LY294002. On the other hand, we found that a MEK inhibitor (PD98059) further enhanced the insulin-stimulated CFTR mRNA expression and the Cl(-) secretion in forskolin-stimulated A6 cells and that insulin induced slight, transient activation of ERK followed by significant inactivation of ERK. These observations suggest that: (1) insulin respectively upregulates mRNA expression of NKCC and CFTR through activation of PI3K and inactivation of ERK; (2) insulin signals on mRNA expression of NKCC and CFTR are not enough to stimulate transepithelial Cl(-) secretion, but enhance the stimulatory action of cAMP on transepithelial Cl(-) secretion.
Akita,
Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system.
2014, Pubmed
Akita,
Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system.
2014,
Pubmed
Aoi,
Improvement of insulin resistance, blood pressure and interstitial pH in early developmental stage of insulin resistance in OLETF rats by intake of propolis extracts.
2013,
Pubmed
Asano,
Quercetin stimulates Na+/K+/2Cl- cotransport via PTK-dependent mechanisms in human airway epithelium.
2009,
Pubmed
Bachmann,
Basolateral ion transporters involved in colonic epithelial electrolyte absorption, anion secretion and cellular homeostasis.
2011,
Pubmed
Banga,
Epinephrine stimulation of anion secretion in the Calu-3 serous cell model.
2014,
Pubmed
Blazer-Yost,
Insulin and IGF I receptor-mediated Na+ transport in toad urinary bladders.
1989,
Pubmed
Blazer-Yost,
Insulin-like growth factor 1 stimulates renal epithelial Na+ transport.
1988,
Pubmed
Blazer-Yost,
Insulin and IGF1 receptors in a model renal epithelium: receptor localization and characterization.
1992,
Pubmed
Bulley,
Cl⁻ channels in smooth muscle cells.
2014,
Pubmed
Butterworth,
Regulation of the epithelial sodium channel by membrane trafficking.
2009,
Pubmed
Chen,
Role of calcium in volume-activated chloride currents in a mouse cholangiocyte cell line.
2007,
Pubmed
Diakov,
Protein kinase B alpha (PKBα) stimulates the epithelial sodium channel (ENaC) heterologously expressed in Xenopus laevis oocytes by two distinct mechanisms.
2010,
Pubmed
,
Xenbase
Diener,
Effects of short-chain fatty acids on cell volume regulation and chloride transport in the rat distal colon.
1997,
Pubmed
Fujii,
Modulation of H(+),K(+)-ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells.
2013,
Pubmed
Fujii,
Inhibition of ecto-ATPase activity by curcumin in hepatocellular carcinoma HepG2 cells.
2012,
Pubmed
Guo,
Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms.
2014,
Pubmed
Handler,
The effect of adrenal steroid hormones on epithelia formed in culture by A6 cells.
1981,
Pubmed
,
Xenbase
Handler,
Hormone effects on transport in cultured epithelia with high electrical resistance.
1981,
Pubmed
,
Xenbase
Hayata,
Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance.
2014,
Pubmed
Hiraoka,
Chloride ion modulates cell proliferation of human androgen-independent prostatic cancer cell.
2010,
Pubmed
Hong,
Mechanism and synergism in epithelial fluid and electrolyte secretion.
2014,
Pubmed
Ikehara,
Luminal trypsin induces enteric nerve-mediated anion secretion in the mouse cecum.
2014,
Pubmed
Ikehara,
Subepithelial trypsin induces enteric nerve-mediated anion secretion by activating proteinase-activated receptor 1 in the mouse cecum.
2012,
Pubmed
Kamynina,
Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na(+) transport.
2002,
Pubmed
Kim,
Role of anion exchangers in Cl- and HCO3- secretion by the human airway epithelial cell line Calu-3.
2014,
Pubmed
Kitagawa,
A regulatory role of K(+)-Cl(-) cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells.
2013,
Pubmed
Lee,
Ca²⁺ signaling and fluid secretion by secretory cells of the airway epithelium.
2014,
Pubmed
Longo,
Insulin stimulates the Na+,K(+)-ATPase and the Na+/K+/Cl- cotransporter of human fibroblasts.
1996,
Pubmed
Maki,
Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells.
2007,
Pubmed
Markadieu,
Hydrogen peroxide and epidermal growth factor activate phosphatidylinositol 3-kinase and increase sodium transport in A6 cell monolayers.
2005,
Pubmed
,
Xenbase
Marunaka,
Protein phosphatase 2B-dependent pathway of insulin action on single Cl- channel conductance in renal epithelium.
1998,
Pubmed
Marunaka,
Effects of insulin and phosphatase on a Ca2(+)-dependent Cl- channel in a distal nephron cell line (A6).
1990,
Pubmed
Marunaka,
Characteristics and Pharmacological Regulation of Epithelial Na+ Channel (ENaC) and Epithelial Na+ Transport.
2014,
Pubmed
Marunaka,
Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6).
1992,
Pubmed
Marunaka,
Roles of Ca2+ and protein tyrosine kinase in insulin action on cell volume via Na+ and K+ channels and Na+/K+/2Cl- cotransporter in fetal rat alveolar type II pneumocyte.
1999,
Pubmed
Marunaka,
Importance of expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells.
2014,
Pubmed
Marunaka,
Regulation of epithelial sodium transport via epithelial Na+ channel.
2011,
Pubmed
Miyazaki,
Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells.
2008,
Pubmed
Mizuno,
Potential role of transient receptor potential (TRP) channels in bladder cancer cells.
2014,
Pubmed
Mohebbi,
Regulation of two renal chloride transporters, AE1 and pendrin, by electrolytes and aldosterone.
2013,
Pubmed
Nakajima,
Enhancement of tubulin polymerization by Cl(-)-induced blockade of intrinsic GTPase.
2012,
Pubmed
Nakajima,
Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na(+)/K(+)/2Cl(-) cotransporter.
2011,
Pubmed
Nakajima,
Essential role of NKCC1 in NGF-induced neurite outgrowth.
2007,
Pubmed
Niisato,
Involvement of cytosolic Cl- in osmoregulation of alpha-ENaC gene expression.
2004,
Pubmed
,
Xenbase
Niisato,
Activation of Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells by flavonoids: genistein, daidzein, and apigenin.
1999,
Pubmed
Niisato,
Hypotonic stress upregulates β- and γ-ENaC expression through suppression of ERK by inducing MKP-1.
2012,
Pubmed
,
Xenbase
Niisato,
Activation of the Na+-K+ pump by hyposmolality through tyrosine kinase-dependent Cl- conductance in Xenopus renal epithelial A6 cells.
1999,
Pubmed
,
Xenbase
Niisato,
Involvement of protein tyrosine kinase in osmoregulation of Na(+) transport and membrane capacitance in renal A6 cells.
2000,
Pubmed
O'Mahony,
Induction of Na+/K+/2Cl- cotransporter expression mediates chronic potentiation of intestinal epithelial Cl- secretion by EGF.
2008,
Pubmed
Ohsawa,
Intracellular chloride regulates cell proliferation through the activation of stress-activated protein kinases in MKN28 human gastric cancer cells.
2010,
Pubmed
Okada,
Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel.
2009,
Pubmed
Okada,
Intracellular mediators of granulysin-induced cell death.
2003,
Pubmed
Panet,
Stimulation of bumetanide-sensitive Na+/K+/Cl- cotransport by different mitogens in synchronized human skin fibroblasts is essential for cell proliferation.
1991,
Pubmed
Perkins,
Transport properties of toad kidney epithelia in culture.
1981,
Pubmed
,
Xenbase
Ponce-Coria,
A novel Ste20-related proline/alanine-rich kinase (SPAK)-independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in the activation of Na-K-Cl cotransporters.
2014,
Pubmed
Sargeant,
Action of insulin on Na(+)-K(+)-ATPase and the Na(+)-K(+)-2Cl- cotransporter in 3T3-L1 adipocytes.
1995,
Pubmed
Schöbel,
Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.
2012,
Pubmed
Shiozaki,
Furosemide, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state.
2006,
Pubmed
Silvis,
Rab11b regulates the apical recycling of the cystic fibrosis transmembrane conductance regulator in polarized intestinal epithelial cells.
2009,
Pubmed
Sun,
Distinct action of flavonoids, myricetin and quercetin, on epithelial Cl⁻ secretion: useful tools as regulators of Cl⁻ secretion.
2014,
Pubmed
,
Xenbase
Takahashi,
Functional coupling of chloride-proton exchanger ClC-5 to gastric H+,K+-ATPase.
2014,
Pubmed
Tse,
Effect of osmotic shrinkage and hormones on the expression of Na+/H+ exchanger-1, Na+/K+/2Cl- cotransporter and Na+/K+ -ATPase in gill pavement cells of freshwater adapted Japanese eel, Anguilla japonica.
2007,
Pubmed
Ueda-Nishimura,
Synergic action of insulin and genistein on Na+/K+/2Cl- cotransporter in renal epithelium.
2005,
Pubmed
,
Xenbase
Zhao,
Signalling mechanisms underlying the rapid and additive stimulation of NKCC activity by insulin and hypertonicity in rat L6 skeletal muscle cells.
2004,
Pubmed
de Los Heros,
The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters.
2014,
Pubmed
