Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways
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 extracellularl...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-10-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520424708 |
| _version_ | 1819077226099900416 |
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| author | Leyre Brizuela Miriam Rábano Patricia Gangoiti Natalia Narbona José María Macarulla Miguel Trueba Antonio Gómez-Muñoz |
| author_facet | Leyre Brizuela Miriam Rábano Patricia Gangoiti Natalia Narbona José María Macarulla Miguel Trueba Antonio Gómez-Muñoz |
| author_sort | Leyre Brizuela |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:53:50Z |
| format | Article |
| id | doaj.art-33f59f3939f24e75911f7e45629169d0 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:53:50Z |
| publishDate | 2007-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-33f59f3939f24e75911f7e45629169d02022-12-21T18:53:41ZengElsevierJournal of Lipid Research0022-22752007-10-01481022642274Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathwaysLeyre Brizuela0Miriam Rábano1Patricia Gangoiti2Natalia Narbona3José María Macarulla4Miguel Trueba5Antonio Gómez-Muñoz6Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, SpainWe 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.http://www.sciencedirect.com/science/article/pii/S0022227520424708adrenal glandceramidemitogen-activated protein kinaseglomerulosa cellsmineralocorticoidsphospholipase D |
| spellingShingle | Leyre Brizuela Miriam Rábano Patricia Gangoiti Natalia Narbona José María Macarulla Miguel Trueba Antonio Gómez-Muñoz Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways Journal of Lipid Research adrenal gland ceramide mitogen-activated protein kinase glomerulosa cells mineralocorticoids phospholipase D |
| title | Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways |
| title_full | Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways |
| title_fullStr | Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways |
| title_full_unstemmed | Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways |
| title_short | Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways |
| title_sort | sphingosine 1 phosphate stimulates aldosterone secretion through a mechanism involving the pi3k pkb and mek erk 1 2 pathways |
| topic | adrenal gland ceramide mitogen-activated protein kinase glomerulosa cells mineralocorticoids phospholipase D |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520424708 |
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