Sphingosine 1-phosphate: a novel stimulator of aldosterone secretion

Brizuela, Leyre; Rábano, Miriam; Peña, Ana; Gangoiti, Patricia; Macarulla, J. M.; Trueba, Miguel; Gómez-Muñoz, Antonio

doi:10.1194/jlr.m500510-jlr200

Cited by 39 publications

(40 citation statements)

References 65 publications

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“…The aim of this work was to evaluate whether the stimulation of aldosterone secretion requires the intervention of signaling mechanisms other than the activation of the PLD/lipid phosphate phosphatase pathway that we described previously (1). Here, we demonstrate for the first time that activation of the PI3K/PKB and MEK/ERK pathways is essential for the stimulation of aldosterone secretion by S1P in isolated cells from the zona glomerulosa (ZG) of adrenal glands.…”

mentioning

confidence: 88%

“…This action involved prior activation of the phospholipase D (PLD)/lipid phosphate phosphatase pathway, Ca 21 influx from the extracellular milieu, and phosphorylation of the protein kinase C (PKC) isoforms a and y (1). S1P has been shown to stimulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) and mitogenactivated kinase kinase (MEK)/extracellularly regulated kinase (ERK) pathways in different cell types.…”

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confidence: 99%

“…Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that regulates critical biological processes, including cell proliferation and survival, cell differentiation, inhibition of tumor cell invasion, migration, cytoskeletal rearrangement, cell contraction, immune responses, and angiogenesis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). S1P can be formed intracellularly and act as a second messenger.…”

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confidence: 99%

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Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Brizuela

Rábano

Gangoiti

et al. 2007

Journal of Lipid Research

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We reported recently that sphingosine-1-phosphate (S1P) is a novel regulator of aldosterone secretion in zona glomerulosa cells of adrenal glands and that phospholipase D (PLD) is implicated in this process. We now show that S1P causes the phosphorylation of protein kinase B (PKB) and extracellularly regulated kinases 1/2 (ERK 1/2), which is an indication of their activation, in these cells. These effects are probably mediated through the interaction of S1P with the Gi protein-coupled receptors S1P1/3, as pretreatment with pertussis toxin or with the S1P1/3 antagonist VPC 23019 completely abolished the phosphorylation of these kinases. Inhibitors of phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase kinase (MEK) blocked S1P-stimulated aldosterone secretion. This inhibition was only partial when the cells were incubated independently with inhibitors of each pathway. However, aldosterone output was completely blocked when the cells were pretreated with LY 294002 and PD 98059 simultaneously. These inhibitors also blocked PLD activation, which indicates that this enzyme is downstream of PI3K and MEK in this system. We propose a working model for S1P in which stimulation of the PI3K/PKB and MEK/ERK pathways leads to the stimulation of PLD and aldosterone secretion.-Brizuela, L., M. Rábano, P. Gangoiti, N. Narbona, J. M. Macarulla, M. Trueba, and A. Gómez-Muñ oz. Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways. J. Lipid Res.

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confidence: 88%

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Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Brizuela

Rábano

Gangoiti

et al. 2007

Journal of Lipid Research

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“…Others have shown that S1P stimulates cortisol secretion in zona fasciculata bovine adrenal cells in a PKC and Ca 2+ -dependent manner (Rabano et al, 2003). In addition to stimulating cortisol secretion, S1P has been recently found to increase aldosterone production via a protein kinase C and phospholipase D-dependent pathway (Brizuela et al, 2006).…”

Section: Bioactive Sphingolipids In Steroidogenesismentioning

confidence: 98%

Steroidogenic factor-1 is a sphingolipid binding protein

Urs

Dammer

Kelly

et al. 2007

Molecular and Cellular Endocrinology

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Steroidogenic factor (SF1, NR5A1, Ad4BP) is an orphan nuclear receptor that is essential for steroid hormone-biosynthesis and endocrine development. Studies have found that the ability of this receptor to increase target gene expression can be regulated by post-translational modification, subnuclear localization, and protein-protein interactions. Recent crystallographic studies and our mass spectrometric analyses of the endogenous receptor have demonstrated an integral role for ligandbinding in the control of SF1 transactivation activity. Herein, we discuss our findings that sphingosine is an endogenous ligand for SF1. These studies and the structural findings of others have demonstrated that the receptor can bind both sphingolipids and phospholipids. Thus, it is likely that multiple bioactive lipids are ligands for SF1 and that these lipids will differentially act to control SF1 activity in a context-dependent manner. Finally, these findings highlight a central role for bioactive lipids as mediators of trophic-hormone stimulated steroid hormone biosynthesis. Keywordssteroidogenic factor-1; CYP17; sphingosine; cAMP; adrenocorticotropin Regulation of SF1 activitySteroid hormone biosynthesis involves the concerted action of a group of proteins that regulate substrate delivery and metabolism. Both the activity and expression of these enzymes is controlled by the integration of signaling pathways. One of these signal transduction pathways involves the activation of the cAMP-dependent protein kinase (PKA). A consequence of PKA activation is increased transcription of steroidogenic genes. This increase in transcription is mediated by the binding of various transcription factors, including SF1, to cAMP responsive sequences in the promoters of steroidogenic genes (Sewer and Waterman, 2001;Sewer and Waterman, 2003). SF1 is a nuclear receptor that plays a key role not only in steroidogenesis (Bakke et al., 2001), but also in endocrine development and sex differentiation (Hammer et al., 2005;Parker et al., 2002).Many laboratories have carried out research to determine the mechanism by which SF1 activates steroidogenic gene transcription. Although transcription of steroidogenic genes Corresponding author: Marion B. Sewer, School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, Tel: (404) Fax: (404) 894-0519; E-mail: marion.sewer@biology.gatech.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Bioactive sphingolipids in steroidogenesisSphingolipids are a diverse family of amphiphatic molecules that are comprised of a long-chain ...

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“…In further studies, a key role of phospholipase D (PLD) in the VLDL response was also demonstrated (Tsai et al 2014), similar to the involvement of this lipid-metabolizing enzyme in AngII-and sphingosine 1-phosphate-induced aldosterone secretion (e.g., Brizuela et al 2006, Qin et al 2010and reviewed in Bollag 2016. Thus, PLD inhibitors reduce VLDL-induced CYP11B2 expression and aldosterone secretion, as does overexpression of lipase-inactive mutants of either PLD1 or PLD2 (Tsai et al 2014).…”

Section: Vldl and Aldosterone Productionmentioning

confidence: 99%

Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

Tsai

Rainey

Bollag

2017

Journal of Endocrinology

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Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure and contributes to cardiovascular and renal disease, stroke and visual loss. Hypertension is also associated with obesity, which is correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear. Several studies have suggested that aldosterone levels are elevated with obesity and may represent a link between obesity and hypertension. In addition to hypertension, obese patients typically have dyslipidemia, including elevated serum levels of very low-density lipoprotein (VLDL). VLDL, which functions to transport triglycerides from the liver to peripheral tissues, has been demonstrated to stimulate aldosterone production. Recent studies suggest that the signaling pathways activated by VLDL are similar to those utilized by AngII. Thus, VLDL increases cytosolic calcium levels and stimulates phospholipase D (PLD) activity to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression. These effects seem to be mediated by the ability of VLDL to increase the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element-binding (CREB) protein family of transcription factors. Thus, research into the pathways by which VLDL stimulates aldosterone production may identify novel targets for the development of therapies for the treatment of hypertension, particularly those associated with obesity, and other aldosterone-modulated pathologies.

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Sphingosine 1-phosphate: a novel stimulator of aldosterone secretion

Cited by 39 publications

References 65 publications

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Steroidogenic factor-1 is a sphingolipid binding protein

Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

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