Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Desagher, Solange; Cordier, Jocelyne; Głowiński, J.; Tencé, Martine

doi:10.1046/j.1471-4159.1997.68010078.x

Cited by 18 publications

(11 citation statements)

References 30 publications

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“…The addition of ET-3 to cultured astrocytes stimulates the expression of cyclooxygenase 2, the production of prostaglandin E 2 [85] and induces the formation of stress fibers, an organized F-actin structure, via a rho-dependent signal cascade [84] and tyrosine phosphorylation of astrocytic proteins [3,84]. In mouse embryo astrocytes that express predominantly ET B receptors, ET-1 induces phospholipase D activation [29], glutamate release [143], stimulation of c-fos and nerve growth factor expression [93], glucose uptake [165] as well as DNA synthesis [24]. At the level of gene expression, ET-1 increases the expression of c-fos in neurons and glia in organotypic culture of rat cerebellum [163] and the expression of m2 and m3 muscarinic acetylcholine receptors in cerebellar granule cells, this latter effect being likely mediated by increased c-fos expression [40].…”

Section: Signal Transduction Pathways Activated By Endothelins In Thementioning

confidence: 99%

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Schinelli¹

2006

CMC

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The endothelin system, consisting of three peptides, two peptidases and two G-protein coupled receptors, is widely expressed in the brain cell types and brain-derived tumor cell lines. The stimulation of endothelin receptors elicits a variety of short- and long-term changes at cellular level but the effects of the pharmacological modulation of the endothelin system in brain physiology and pathophysiology are, at the present time, poorly understood. Altered expression of endothelins (ETs) in reactive astrocytes has been observed in many pathological conditions of the human brain, such as infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain. In addition, recent studies have shown that endothelin antagonists might inhibit growth and induce cell death in human melanoma cells in vitro and in vivo, and have emphasized a possible role of endothelin peptides as autocrine or paracrine factor in the proliferation and dissemination of tumor cell lines. Given the fact that brain cell and a variety of brain tumor cell lines express functional endothelin receptors, further studies are warranted to demonstrate a possible therapeutic role of endothelin agonists and antagonist in the pharmacological treatment of brain-related diseases and brain tumors.

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Section: Signal Transduction Pathways Activated By Endothelins In Thementioning

confidence: 99%

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Schinelli¹

2006

CMC

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“…Astrocytes express endothelin receptors (of the B subtype), which are functionally coupled via heterotrimeric G proteins to several intracellular pathways. The stimulation of these receptors induces a marked and persistent increase in cytosolic Ca2 ( Mann et al, 1991), the activation of phospholipases C (MacCumber et a!., 1990;Stanimirovic et a!., 1995) and D (Desagher et al, 1997), and the inhibition of adenylyl cyclase activity (Mann et a!., 1991). Thus, the exposure of astrocytes to endothelins may result in the activation of PKC, mitogen-activated protein kinase and FAK/Src pathways, and in the inhibition of cyclic AMP-dependent protein kinase (Cazaubon et al, 1994(Cazaubon et al, , 1997.…”

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confidence: 99%

Endothelin Induces a Calcium‐Dependent Phosphorylation of PEA‐15 in Intact Astrocytes: Identification of Ser¹⁰⁴ and Ser¹¹⁶ Phosphorylated, Respectively, by Protein Kinase C and Calcium/Calmodulin Kinase II In Vitro

Kubeš

Cordier

Głowiński

et al. 1998

Journal of Neurochemistry

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PEA‐15 (phosphoprotein enriched in astrocytes, Mr = 15,000) is an acidic serine‐phosphorylated protein highly expressed in the CNS, where it can play a protective role against cytokine‐induced apoptosis. PEA‐15 is a major substrate for protein kinase C. Endothelins, which are known to exert pleiotropic effects on astrocytes, were used to analyze further the processes involved in PEA‐15 phosphorylation. Endothelin‐1 or endothelin‐3 (0.1 µM) induced a robust phosphorylation of PEA‐15 that was abolished by the removal of extracellular calcium, but only diminished by inhibitors of protein kinase C. Microsequencing of phosphopeptides generated by digestion of PEA‐15 following endothelin‐1 treatment identified two phosphorylated residues: Ser104, previously recognized as the protein kinase C site, and a novel phosphoserine, Ser116, located in a consensus motif for either protein kinase casein kinase II or calcium/calmodulin‐dependent protein kinase II (CaMKII). Partly purified PEA‐15 was a substrate in vitro for CaMKII, but not for casein kinase II. Two‐dimensional phosphopeptide mapping demonstrated that the site phosphorylated in vitro by CaMKII was also phosphorylated in intact astrocytes in response to endothelin. CaMKII phosphorylated selectively Ser116 and had no effect on Ser104, but in vitro phosphorylation by CaMKII appeared to facilitate further phosphorylation by protein kinase C. Treatment of intact astrocytes with okadaic acid enhanced the phosphorylation of the CaMKII site. These results demonstrate that PEA‐15 is phosphorylated in astrocytes by CaMKII (or a related kinase) and by protein kinase C in response to endothelin.

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“…In a variety of cell types, endothelin receptors activate PLD [1, 2, 7, 14], an enzyme which uses PC as a substrate to produce PA [2, 14]. To determine whether PLD mediates inhibition of ENaC by endothelin, we performed cell-attached experiments.…”

Section: Resultsmentioning

confidence: 99%

Anionic phospholipids differentially regulate the epithelial sodium channel (ENaC) by interacting with α, β, and γ ENaC subunits

Zhang

Chou

Wang

et al. 2009

Pflugers Arch - Eur J Physiol

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Anionic phospholipids (APs) present a variety of lipids in the cytoplasmic leaflet of the plasma membrane, including phosphatidylinositol (PI), PI-4-phosphate (PI(4) P), phosphatidylserine (PS), PI-4,5-bisphosphate (PI(4,5) P 2 ), PI-3,4,5-trisphosphate (PI(3,4,5)P 3 ), and phosphatidic acid (PA). We previously showed that PI(4,5)P 2 and PI(3,4,5)P 3 upregulate the renal epithelial sodium channel (ENaC). Further studies from others suggested that PI(4,5) P 2 and PI(3,4,5)P 3 respectively target β-and γ-ENaC subunit. To determine whether PI(4,5)P 2 and PI(3,4,5)P 3 selectively bind to β and γ subunit, we performed lipid-protein overlay experiments. Surprisingly, the results reveal that most APs, including PI(4)P, PS, PI(4,5)P 2 , PI(3,4,5)P 3 , and PA, but not PI, non-selectively bind to not only β and γ but also α subunit. To determine how these APs regulate ENaC, we performed insideout patch-clamp experiments and found that PS, but not PI or PI(4)P, maintained ENaC activity, that PI(4,5)P 2 and PI(3,4,5)P 3 stimulated ENaC, and that PA, however, inhibited ENaC. These data together suggest that APs differentially regulate ENaC by physically interacting with α-, β-, and γ-ENaC. Further, the data from cell-attached patch-clamp and confocal microscopy experiments indicate that PA, a product of phospholipase D, may provide one of the pathways for inhibition of ENaC by endothelin receptors.

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Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Cited by 18 publications

References 30 publications

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Endothelin Induces a Calcium‐Dependent Phosphorylation of PEA‐15 in Intact Astrocytes: Identification of Ser¹⁰⁴ and Ser¹¹⁶ Phosphorylated, Respectively, by Protein Kinase C and Calcium/Calmodulin Kinase II In Vitro

Anionic phospholipids differentially regulate the epithelial sodium channel (ENaC) by interacting with α, β, and γ ENaC subunits

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Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Cited by 18 publications

References 30 publications

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Endothelin Induces a Calcium‐Dependent Phosphorylation of PEA‐15 in Intact Astrocytes: Identification of Ser104 and Ser116 Phosphorylated, Respectively, by Protein Kinase C and Calcium/Calmodulin Kinase II In Vitro

Anionic phospholipids differentially regulate the epithelial sodium channel (ENaC) by interacting with α, β, and γ ENaC subunits

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Endothelin Induces a Calcium‐Dependent Phosphorylation of PEA‐15 in Intact Astrocytes: Identification of Ser¹⁰⁴ and Ser¹¹⁶ Phosphorylated, Respectively, by Protein Kinase C and Calcium/Calmodulin Kinase II In Vitro