Expression of Endothelin and ETB Receptors in the Megakaryoblastic MEG-01 Cell Line

Hamroun, Dalil; Mathieu, M; Clain, Elodie; Germani, Elodie; Laliberté, Marie-France; Laliberté, François; Chevillard, Claude

doi:10.1097/00005344-199506263-00049

Cited by 4 publications

(2 citation statements)

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“…Although the ET a receptor expressed in smooth muscle is generally observed to be Gα q coupled to changes in [Ca 2+ ] i and intracellular diacylglycerol ( 15 , 16 ), we found that pre-treatment of HPASMC with the ET a receptor antagonist BQ123 ( 17 ) or the dual specific ET a /ET b antagonist Bosentan ( 18 ) ( Fig. 1 D ) was more effective at inhibiting ET-1-induced cAMP synthesis than the ET b selective antagonist BQ788 ( 19 ) implying that ET-1-stimulated cAMP synthesis is mainly via the ET a receptor.…”

Section: Resultsmentioning

confidence: 78%

Endothelin-1 (ET-1) Increases the Expression of Remodeling Genes in Vascular Smooth Muscle through Linked Calcium and cAMP Pathways

Deacon

Knox

2010

Journal of Biological Chemistry

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Several important genes that are involved in inflammation and tissue remodeling are switched on by virtue of CRE response elements in their promoters. The upstream signaling mechanisms that inflammatory mediators use to activate cAMP response elements (CREs) are poorly understood. Endothelin (ET) is an important vasoactive mediator that plays roles in inflammation, vascular remodeling, angiogenesis, and carcinogenesis by activating 7 transmembrane G protein-coupled receptors (GPCR). Here we characterized the mechanisms ET-1 uses to regulate CRE-dependent remodeling genes in pulmonary vascular smooth muscle cells. These studies revealed activation pathways involving a cyclooxygenase-2 (COX-2)/prostacyclin receptor (IP receptor) autocrine loop and an interlinked calcium-dependent pathway. We found that ET-1 activated several CRE response genes in vascular smooth muscle cells, particularly COX-2, amphiregulin, follistatin, inhibin-β-A, and CYR61. ET-1 also activated two other genes epiregulin and HB-EGF. Amphiregulin, follistatin, and inhibin-β-A and epiregulin were activated by an autocrine loop involving cPLA2, arachidonic acid release, COX-2-dependent PGI2 synthesis, and IP receptor-linked elevation of cAMP leading to CRE transcription activation. In contrast COX-2, CYR61, and HB-EGF transcription were regulated in a calcium-dependent, COX-2 independent, manner. Observations with IP receptor antagonists and COX-2 inhibitors were confirmed with IP receptor or COX-2-specific small interfering RNAs. ET-1 increases in intracellular calcium and gene transcription were dependent upon ETa activation and calcium influx through T type voltage-dependent calcium channels. These studies give important insights into the upstream signaling mechanisms used by G protein-coupled receptor-linked mediators such as ET-1, to activate CRE response genes involved in angiogenesis, vascular remodeling, inflammation, and carcinogenesis.

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Section: Resultsmentioning

confidence: 78%

Endothelin-1 (ET-1) Increases the Expression of Remodeling Genes in Vascular Smooth Muscle through Linked Calcium and cAMP Pathways

Deacon

Knox

2010

Journal of Biological Chemistry

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“…Many studies have suggested that not only platelet precursor cell lines, e.g., HEL, MEG-01 and DAMI cells but also the normal human platelet progenitors themselves express ET A and ET B (both ET receptors), preproendothelin-1 mRNA, functional phosphoramidon-sensitive and insensitive endothelin converting enzyme activity which finally produce mature ET (Mathieu et al, 1997;Mathieu et al, 1998). Hamroun et al (1995) reported that an ET-1 mediated Accepted: 12 January, 2001 autocrine loop could occur in the human megakaryoblastic MEG-01 cell line. In another study ET-1 was found to induce an increase in the accumulation of inositol 1,4,5-triphosphate and elevation of intracellular levels of Ca 2+ (Diochot et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

The Mitogenic Activity of Endothelin-1 on Megakaryocytopoiesis In Vitro

Kabadere

Uzuner

Altuner

et al. 2001

Archives of Physiology and Biochemistry

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Endothelin (ET)-1 induces proliferation of various cells including smooth muscle cells, fibroblasts, glomerular mesangial cells, endothelial cells and osteoblasts. ET-1 also stimulates synthesis of interleukin (IL)-6 in endothelial and bone marrow stromal cells of rat. It is well known that IL-6 modulates megakaryocytopoiesis. Some studies have indicated that megakaryocytes express both ET receptors and they are targets for ET. Therefore we planned to examine the effects of ET-1 on the growth of normal megakaryocytic cells in rat bone marrow primary cell culture. Bone marrow cells were cultured at 37 degrees C, in an incubator atmosphere of 5% CO2 in air and 95% relative humidity for nine days. ET-1 at 10(-7), 10(-8 ) and 10(-11) M, and control with saline were added at the beginning of the experiment protocol. At each day, plasma clots were stained using direct-coloring thiocholin method for acetylcholinesterase activity. Although 10(-7) M ET-1 did not change the proliferation of megakaryocytic cells, this could be due to the presence of over crowded fibroblasts in the same environment. 10(-8) M ET-1 stimulated megakaryocytic cell growth to 234% over the control on the fifth day. ET-1 at a concentration of 10(-11) M also rised the megakaryocytic cell number significantly reaching up to 86% at the sixth day. Our results indicate that ET-1 may modulate the growth of megakaryocytic cells by an autocrine and/or paracrine action.

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An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo

Lahav

Heffner

Patterson

1999

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

137

119

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Activation of the endothelin receptor B (ETRB) in cultured melanocyte precursors promotes cell proliferation while inhibiting differentiation, two hallmarks of malignant transformation. We therefore tested whether ETRB has a similar role in malignant transformation of melanoma. When tested in culture, we find that the selective ETRB antagonist BQ788 can inhibit the growth of seven human melanoma cell lines, but not a human kidney cell line. This inhibition often is associated with increases in pigmentation and in the dendritic shape that is characteristic of mature melanocytes. In three cell lines we also observe a major increase in cell death. In contrast, the endothelin receptor A (ETRA) antagonist BQ123 does not have these effects, although all the cell lines express both ETRA and ETRB mRNA. Extending these studies in vivo, we find that administration of BQ788 significantly slows human melanoma tumor growth in nude mice, including a complete growth arrest in half of the mice treated systemically. Histological examination of tumor sections suggests that BQ788 also enhances melanoma cell death in vivo. Thus, ETRB inhibitors may be beneficial for the treatment of melanoma.

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Expression of Endothelin and ETB Receptors in the Megakaryoblastic MEG-01 Cell Line

Cited by 4 publications

References 0 publications

Endothelin-1 (ET-1) Increases the Expression of Remodeling Genes in Vascular Smooth Muscle through Linked Calcium and cAMP Pathways

Endothelin-1 (ET-1) Increases the Expression of Remodeling Genes in Vascular Smooth Muscle through Linked Calcium and cAMP Pathways

The Mitogenic Activity of Endothelin-1 on Megakaryocytopoiesis In Vitro

An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo

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