New aspects of rapid aldosterone signaling

Großmann, Claudia; Gekle, Michael

doi:10.1016/j.mce.2009.02.005

Cited by 118 publications

(105 citation statements)

References 149 publications

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“…Previous studies implicate posttranslational phosphorylation associated with NKCC1 expression changes (1,9,23,25,29,44,50). In contrast, the present investigation is the first report that ALD exerts its effects on NKCC1 expression via prevention of posttranslational ubiquitination, e.g., reduces proteasome-dependent degradation of the NKCC1 protein.…”

Section: Discussioncontrasting

confidence: 50%

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Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Ding

Frisina

Liu

et al. 2014

American Journal of Physiology-Cell Physiology

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Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na+ and K+ concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.

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Section: Discussioncontrasting

confidence: 50%

“…Stimulation of NKCC1 increases Na ϩ , K ϩ , and Cl Ϫ fluxes, as previously noted (16,17,23,28,49,54). Ion flux assays represent functional assays that measure efflux of ions through cotransporters such as NKCC1.…”

Section: Discussionmentioning

confidence: 64%

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Ding

Frisina

Liu

et al. 2014

American Journal of Physiology-Cell Physiology

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“…9cRA reportedly stimulates phosphorylation of p38 mitogen-activated protein kinase (37). Recent work has shown that atRA has rapid, nongenomic actions on neurite outgrowth and endothelial cell growth (38, 39)-indicating that retinoids, like several steroid hormones, do not solely regulate transcription (40)(41)(42)(43). The acute, nongenomic effects reported here for 9cRA differ from the effects of synthetic RXR analogs, known as rexinoids, in rodent diabetic models (44).…”

Section: Discussionmentioning

confidence: 66%

Identification of 9- cis -retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion

Kane

Folias

Pingitore

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

103

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The all-trans-retinoic acid (atRA) isomer, 9-cis-retinoic acid (9cRA), activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in vitro. RARs control multiple genes, whereas RXRs serve as partners for RARs and other nuclear receptors that regulate metabolism. Physiological function has not been determined for 9cRA, because it has not been detected in serum or multiple tissues with analytically validated assays. Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat β-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4α mRNA expression, ∼8-and 80-fold, respectively: defects in Pdx-1 or HNF4α cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2). Pancreas β-cells generate 9cRA, and mouse models of reduced β-cell number, heterozygous Akita mice, and streptozotocin-treated mice have reduced 9cRA. 9cRA is abnormally high in glucose-intolerant mice, which have β-cell hypertropy, including mice with diet-induced obesity (DIO) and ob/ob and db/db mice. These data establish 9cRA as a pancreas-specific autacoid with multiple mechanisms of action and provide unique insight into GSIS.retinol | vitamin A | rexinoids I mpaired glucose-stimulated insulin secretion (GSIS) develops through multiple mechanisms, including actions of metabolic hormones and inflammatory cytokines, products of metabolic overload, and endoplasmic reticulum stress; however, mechanisms of GSIS and impaired glucose tolerance remain incompletely understood (1-4). Also uncertain is the contribution of impaired glucose tolerance to diminished pancreatic β-cell function and mass associated with type 2 diabetes (5). GSIS relies on the pancreas, and pancreas development, islet formation, and function require normal vitamin A nutriture (6-8). Vitamin A restriction during development impairs islet development and promotes glucose intolerance in adult rodents. On the other hand, restricting vitamin A in mature diabetes-prone rats reduces diabetes and insulitis, possibly through enhancing glucose sensing and metabolism. Alltrans-retinoic acid (atRA), an activated metabolite of vitamin A, regulates pancreas development, and atRA does not enhance the incidence of diabetes in diabetes-prone rats fed a vitamin Adeficient diet (7, 9, 10). Although the contribution of vitamin A to pancreas development through atRA seems clear, mechanisms whereby vitamin A affects mature pancreas function have not been determined in depth, nor have the specific vitamin A metabolites been identified that contribute to GSIS control.atRA induces differentiation and regulates cell processes by activating the nuclear receptors RAR α, -β, and -γ, which regulate transcription and translation (11...

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“…For example, multiple studies have proven involvement of G-proteins and the signal-regulated kinase-CREB pathway. Importantly, these same pathways are also activated by rapid signalling of other steroid receptors, such as the oestrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR; reviewed in (Hammes & Levin 2007, Vasudevan & Pfaff 2007, Levin 2008) and by rapid aldosterone signalling through the MR in peripheral tissues (Grossmann & Gekle 2009). Information gathered in these related fields could serve as an important guideline for investigation of the signalling partners of corticosteroids in the brain.…”

Section: Discussionmentioning

confidence: 99%

Rapid non-genomic effects of corticosteroids and their role in the central stress response

Groeneweg¹,

Karst²,

Kloet³

et al. 2011

Journal of Endocrinology

364

269

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In response to a stressful encounter, the brain activates a comprehensive stress system that engages the organism in an adaptive response to the threatening situation. This stress system acts on multiple peripheral tissues and feeds back to the brain; one of its key players is the family of corticosteroid hormones. Corticosteroids affect brain functioning through both delayed, genomic and rapid, non-genomic mechanisms. The latter mode of action has long been known, but it is only in recent years that the physiological basis in the brain is beginning to be unravelled. We now know that corticosteroids exert rapid, non-genomic effects on the excitability and activation of neurons in (amongst others) the hypothalamus, hippocampus, amygdala and prefrontal cortex. In addition, corticosteroids affect cognition, adaptive behaviour and neuroendocrine output within minutes. Knowledge on the identity of the receptors and secondary pathways mediating the non-genomic effects of corticosteroids on a cellular level is accumulating. Interestingly, in many cases, an essential role for the 'classical' mineralocorticoid and glucocorticoid receptors in a novel membrane-associated mechanism is found. Here, we systematically review the recent literature on non-genomic actions of corticosteroids on neuronal activity and functioning in selected limbic brain targets. Further, we discuss the relevance of these permissive effects for cognition and neuroendocrine control, and the integration of this novel mode of action into the complex balanced pattern of stress effects in the brain.

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New aspects of rapid aldosterone signaling

Cited by 118 publications

References 149 publications

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Identification of 9- cis -retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion

Rapid non-genomic effects of corticosteroids and their role in the central stress response

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New aspects of rapid aldosterone signaling

Cited by 118 publications

References 149 publications

Direct control of Na+-K+-2Cl−-cotransport protein (NKCC1) expression with aldosterone

Direct control of Na+-K+-2Cl−-cotransport protein (NKCC1) expression with aldosterone

Identification of 9- cis -retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion

Rapid non-genomic effects of corticosteroids and their role in the central stress response

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Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone

Direct control of Na⁺-K⁺-2Cl⁻-cotransport protein (NKCC1) expression with aldosterone