Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia.

Giaid, Adel; Gibson, Susan E.; Ibrahim, N. B. N.; Legon, S.; Bloom, Stephen R.; Yanagisawa, Masashi; Masaki, Τοmoh; Varndell, Ian M.; Polak, Julia M.

doi:10.1073/pnas.86.19.7634

Cited by 308 publications

(140 citation statements)

References 14 publications

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“…The sequence of preproET-1 deleted in Stop9l contains a cysteine-rich ET-1-like domain of 15 amino acids with 8 conserved residues. It has been suggested that ET-1 might have an endocrine function as a neuropeptide or neuromodulator (19) and could be stored in secretory granules in the posterior pituitary (20). ET-1 is encoded by a single gene (21) and is expressed in widely different cell types (2), some of which are endowed with a regulated secretory pathway.…”

Section: Discussionmentioning

confidence: 99%

In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site.

Fabbrini

Vitale

Nitti

et al. 1993

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

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Endothelin-1 (ET-1), a 21-residue vasoconstrictor peptide, originates in human cells from a 212-amino acid precursor (preproET-1). Big ET-1, an intermediate form of 38 amino acids, is generated by cleavage at basic-pair residues of proET-1, while a specific "ET-converting enzyme" was proposed to process the unusual Trp-Val site at positions 21 and 22 of big ET-1. We have previously shown that expression of synthetic RNA encoding human preproET-1 in Xenopus oocytes results in secretion of putative ET-1 and big ET-1. Here, to further dissect the processing pathway of preproET-1, we designed and expressed in oocytes a set of preproET-1 mutants. Four mutants affecting the Trp-Val site always originated putative ET-1(s) at levels comparable to the wild type, suggesting that there is only a conformational requirement for cleavage at this site. An Arg --Ile mutation at the basic-pair site after the C terminus of big ET-1 fully inhibited the formation of both big ET-1 and ET-1, indicating that processing at this site is an early event and that big ET-1 is an obligate intermediate for the synthesis of ET-1 in vivo. Also, a truncated mutant bearing a stop codon after the C terminus of the big ET-1 sequence was totally stable and further processed into mature big ET-1 and ET-1, indicating that the second part of the precursor is not necessary for maturation.The 21-residue vasoconstrictor peptide human endothelin-1 (ET-1), like many growth factors and peptide hormones, is first synthesized as a larger inactive precursor (preproET-1, see Fig. 1) (1). While ET-1 seems to exert a wide range of diverse biological activities (2), the 38-amino acid intermediate big ET-1 is at least 2 orders of magnitude less potent than ET-1 in contractile activity, and it is still not clear whether it plays some pathophysiologic role. Many efforts have been made to search for a specific endothelinconverting enzyme (ECE) responsible for the cleavage of the unusual Trp-Val site of big ET-1 as a key element in the regulation of ET-1 biosynthesis (3, 4). However, expression of human preproET-1 in Xenopus oocytes (5) or insect cells (6) results in constitutive secretion of peptides with immunological and biological characteristics of ET-1 and big ET-1.For further study of the processing events and molecular requirements leading to big ET-1 and ET-1 formation, we report expression of a set of mutated preproendothelins in Xenopus oocytes. We demonstrate that big ET-1 is a necessary intermediate in the formation of ET-1, whereas the second part of preproET-1 (after the C terminus of big ET-1) is not necessary for the synthesis of these two peptides.

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Section: Discussionmentioning

confidence: 99%

In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site.

Fabbrini

Vitale

Nitti

et al. 1993

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

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“…High-affinity receptor sites for ET are found in the central nervous system (Giaid et al, 1989;Jones et al, 1989;Koseki et al, 1989) and ET-mediated Ca2+ responses have been demonstrated in neurons as well as in glial cells in culture (Fu et al, 1989;Supattapone et al, 1989;Lin et al, 1990a;MacCumber et al, 1990;Marsault et a]., 1990;Stojilkovic et al, 1990;Zhang et al, 1990). Studies by MacCumber et al (1 990) have suggested that ET in brain is produced largely by the glial cells, but it can act on both glia and neurons in a paracrine fashion.…”

mentioning

confidence: 99%

Endothelin‐Mediated Calcium Response and Inositol 1,4,5‐Trisphosphate Release in Neuroblastoma‐Glioma Hybrid Cells (NG108‐15): Cross Talk with ATP and Bradykinin

Chau

Lin

Chang

et al. 1993

Journal of Neurochemistry

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“…ET-1, başlıca damar endotelinde sentezlenlenip salıverilmekte ve burada damar geriminin düzenlenmesini sağlamaktadır. Bunun dışında, mast hücreleri, makrofajlar, mukozal epiteliyum, kardiyomiyositler, nöronlar, trakea epiteli, renal medulla, hepatik sinüzoitler ve Kuppfer hücrelerinde de sentezlenmektedir (39)(40)(41)(42)(43)(44). Vücutta daha az dağılım gösteren ET-2 böbrek ve bağırsaklarda bulunurken; ET-3 ise beyin, akciğer, bağırsak ve adrenal bezde bulunmaktadır (45)(46).…”

Section: Toll-interleukin 1 Receptor Domain-containing Adapter-induciunclassified

The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

Guden¹,

Temiz²,

Tunçtan³

et al. 2015

MUSBED

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Sepsis ve septik şok patojenezinde endotelin-1'in rolü ve tedavide yeni yaklaşımlar Vücuda giren patojene karşı gelişen sistemik enflamatuvar yanıt olarak adlandırılan sepsis, septik şok, çoklu organ yetmezliği ve ölümle sonuçlanabilmektedir. Sistemik enflamatuvar yanıtı tetikleyebilen artmış proenflamatuvar sitokin düzeyleriyle birlikte kemokinler, koagülasyon ve kompleman sistemleri ile vazoaktif aminler de sepsis patojenezinde yer almaktadır. Endotelin (ET)-1, 1988 yılında vazoaktif amin olarak damar endotelinden izole edilmiş olup 21 zincirli amino asit zincirine sahip bir peptitdir. (ET)-1'in sepsis ve septik şok gelişimindeki rolü deneysel ve klinik çalışmalarda gösterilmiş olup, reseptör antagonistleri sepsis tedavisinde denenmiş ve yararlı sonuçlar sağlamıştır. ET-1'in mitojenle etkinleştirilen protein kinaz sinyal ileti yolunu uyararak etkinleştirdiği downstream sinyal molekülleri aracılığıyla reaktif oksijen türlerinin üretiminde artış, enflamasyon gelişimi, endotelyal işlevde bozulma, anormal damar gerimi ve damarlarda yeniden modellenme gibi olaylara yol açarak sepsis, septik şok ve çoklu organ yetmezliği gelişiminde önemli rolü olabileceği düşünülmektedir.

show abstract

Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia.

Cited by 308 publications

References 14 publications

In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site.

In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site.

Endothelin‐Mediated Calcium Response and Inositol 1,4,5‐Trisphosphate Release in Neuroblastoma‐Glioma Hybrid Cells (NG108‐15): Cross Talk with ATP and Bradykinin

The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

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