Transient hypoxia/hypoglycemia upregulates endothelin B receptors in cultured rat astrocytes

Shibaguchi, Hirotomo; Himeno, Akihiko; Shigematsu, Kazuto; Kataoka, Yasufumi; Níwa, Masami

doi:10.1002/(sici)1098-1136(200007)31:1<91::aid-glia90>3.0.co;2-e

Cited by 11 publications

(1 citation statement)

References 27 publications

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“…No HRE has yet been described in the promoter of either endothelin receptor, but in certain cell types, both receptors may be induced by hypoxia (Shibaguchi et al 2000, Grimshaw et al 2002b). This may, however, be a secondary effect due to the increase in endothelin production seen under hypoxic conditions: endothelins themselves induce endothelin receptor production by breast carcinoma cells (Grimshaw et al 2004).…”

Section: Endothelins and Hif-1mentioning

confidence: 99%

Endothelins and hypoxia-inducible factor in cancer

Grimshaw¹

2007

Endocr Relat Cancer

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The endothelin system is a family of three similar small peptides, two G-protein-coupled receptors and two proteinases. Endothelins have several physiological roles, notably in embryonic differentiation and vascular homeostasis. Numerous types of tumour express endothelins and their regulation is often aberrant when compared with the normal tissue from which the tumour arose. However, endothelin expression is tumour-type specific, and in some instances, expression of individual members of the endothelin system will be upregulated, while in other tumour types, they may be downregulated. Endothelins have numerous potential roles in tumours including modulating angiogenesis, inducing mitogenesis and invasion of tumour cells, and protecting cells from apoptosis. Expression of endothelins is controlled by the tumour microenvironment, whilst the endothelins themselves modify that environment; a case in point is that hypoxia stimulates endothelin expression via hypoxia-inducible factor (HIF)-1, while endothelins stabilise HIF-1 leading to expression of, for instance, vascular endothelial growth factor. This review highlights the potential roles of endothelins in various cancers and describes the pre-clinical and clinical progress that has been made in several tumour types -notably prostate, ovary, melanoma and breast cancer. The interactions between the endothelin network and HIF-1 are highlighted.

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Section: Endothelins and Hif-1mentioning

confidence: 99%

Endothelins and hypoxia-inducible factor in cancer

Grimshaw¹

2007

Endocr Relat Cancer

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Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS

Rogers

Peters

Pomonis

et al. 2002

Glia

100

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The ability of mammalian central nervous system (CNS) neurons to survive and/or regenerate following injury is influenced by surrounding glial cells. To identify the factors that control glial cell function following CNS injury, we have focused on the endothelin B receptor (ET(B)R), which we show is expressed by the majority of astrocytes that are immunoreactive for glial acid fibrillary protein (GFAP) in both the normal and crushed rabbit optic nerve. Optic nerve crush induces a marked increase in ET(B)R and GFAP immunoreactivity (IR) without inducing a significant increase in the number of GFAP-IR astrocytes, suggesting that the crush-induced astrogliosis is due primarily to astrocyte hypertrophy. To define the role that endothelins play in driving this astrogliosis, artificial cerebrospinal fluid (CSF), ET-1 (an ET(A)R and ET(B)R agonist), or Bosentan (a mixed ET(A)R and ET(B)R antagonist) were infused via osmotic minipumps into noninjured and crushed optic nerves for 14 days. Infusion of ET-1 induced a hypertrophy of ET(B)R/GFAP-IR astrocytes in the normal optic nerve, with no additional hypertrophy in the crushed nerve, whereas infusion of Bosentan induced a significant decrease in the hypertrophy of ET(B)R/GFAP-IR astrocytes in the crushed but not in the normal optic nerve. These data suggest that pharmacological blockade of astrocyte ET(B)R receptors following CNS injury modulates glial scar formation and may provide a more permissive substrate for neuronal survival and regeneration.

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Role of the astrocytic ET_B receptor in the regulation of extracellular endothelin‐1 during hypoxia

Hasselblatt

Lewczuk

Löffler

et al. 2001

Glia

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Astrocytes are known to possess an effective endothelin (ET) eliminatory system which involves astrocytic ET(A) and ET(B) receptors and may become particularly relevant under pathophysiological conditions. The present study has therefore been designed to explore the effect of standardized hypoxia on extracellular concentrations of endothelin-1 (ET-1) and on endothelin-converting enzyme (ECE) activity in primary rat astrocytes genetically (sl/sl) or experimentally (dexamethasone) deficient in ET(B) receptors. The results revealed (1) a hypoxia-mediated decrease of extracellular ET-1 in wildtype astrocytes (+/+) that was not observed in ET(B)-deficient (sl/sl) cultures; (2) an ET receptor antagonist-induced increase in ET-1 in the media of both genotypes with further elevation upon hypoxia in +/+ cultures only; (3) augmentation of the dexamethasone-induced increase in extracellular ET-1 by hypoxia in +/+, but not in sl/sl cultures; (4) synergistic reduction of ET(B) gene transcription by hypoxia and dexamethasone; and (5) significant increases in endothelin-converting enzyme activity in the presence of hypoxia. To conclude, hypoxia stimulates astrocytic release of mature ET-1. This stimulation is (over)compensated for by increased ET-1 binding to functional ET(B) receptors. ET(B) deficiency, whether genetic or experimentally induced, impairs elimination of extracellular ET-1.

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Transient hypoxia/hypoglycemia upregulates endothelin B receptors in cultured rat astrocytes

Cited by 11 publications

References 27 publications

Endothelins and hypoxia-inducible factor in cancer

Endothelins and hypoxia-inducible factor in cancer

Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS

Role of the astrocytic ET_B receptor in the regulation of extracellular endothelin‐1 during hypoxia

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Transient hypoxia/hypoglycemia upregulates endothelin B receptors in cultured rat astrocytes

Cited by 11 publications

References 27 publications

Endothelins and hypoxia-inducible factor in cancer

Endothelins and hypoxia-inducible factor in cancer

Endothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNS

Role of the astrocytic ETB receptor in the regulation of extracellular endothelin‐1 during hypoxia

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Role of the astrocytic ET_B receptor in the regulation of extracellular endothelin‐1 during hypoxia