Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/11/09 10:18:47」(JST)

wiki en

Endothelin 2
Identifiers
Symbol	EDN2
Entrez	1907
HUGO	3177
OMIM	131241
RefSeq	NM_001956
UniProt	P20800
Other data
Locus	Chr. 1 p34

Endothelin 3
Identifiers
Symbol	EDN3
HUGO	3178
OMIM	131242
RefSeq	NM_000114
UniProt	P14138
Other data
Locus	Chr. 20 q13.2-q13.3

Endothelins are peptides that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure (hypertension) and heart disease.

Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. Endothelins are implicated in vascular diseases of several organ systems, including the heart, general circulation and brain.^[1]^[2]

Etymology

Endothelins derived the name from the fact that they were derived and secreted from cultured endothelial cells.^[3]

Isoforms

There are three isoforms (identified as ET-1, -2, -3) with varying regions of expression and binding to at least four known endothelin receptors, ET_A, ET_B1, ET_B2 and ET_C.^[4]

Antagonists

Earliest antagonists discovered for ET_A is BQ123, and that for ET_B is BQ788.^[3]

Examples of physiological interaction

Endothelins are the most potent vasoconstrictors known.^[5] In a healthy individual, a delicate balance between vasoconstriction and vasodilation is maintained by endothelin and other vasoconstrictors on the one hand and nitric oxide, prostacyclin and other vasodilators on the other.

Overproduction of endothelin in the lungs may cause pulmonary hypertension, which can sometimes be treated by the use of an endothelin receptor antagonist, such as bosentan, sitaxentan or ambrisentan. The latter drug selectively blocks endothelin A receptors, decreasing the vasoconstrictive actions and allowing for increased beneficial effects of endothelin B stimulation, such as nitric oxide production. The precise effects of endothelin B receptor activation depends on the type of cells involved.

Disease involvement

The ubiquitous distribution of endothelin peptides and receptors implicates its involvement in a wide variety of physiological and pathological processes in the body. Among numerous diseases potentially occurring from endothelin dysregulation are

several types of cancer^[6]
cerebral vasospasm following subarachnoid hemorrhage^[7]
arterial hypertension and other cardiovascular disorders
pain mediation^[8]
cardiac hypertrophy
Dengue haemorrhagic fever
Type II diabetes
some cases of Hirschsprung disease

Gene regulation

The endothelium regulates local vascular tone and integrity through the coordinated release of vasoactive molecules. Secretion of endothelin-1 (ET-1)1 from the endothelium signals vasoconstriction and influences local cellular growth and survival. ET-1 has been implicated in the development and progression of vascular disorders such as atherosclerosis and hypertension. Endothelial cells upregulate ET-1 in response to hypoxia, oxidized LDL, pro-inflammatory cytokines, and bacterial toxins. Initial studies on the ET-1 promoter provided some of the earliest mechanistic insight into endothelial-specific gene regulation. Numerous studies have since provided valuable insight into ET-1 promoter regulation under basal and activated cellular states.

The ET-1 mRNA is labile with a half-life of less than an hour. Together, the combined actions of ET-1 transcription and rapid mRNA turnover allow for stringent control over its expression. It has previously been shown that ET-1 mRNA is selectively stabilized in response to cellular activation by Escherichia coli O157:H7-derived verotoxins, suggesting ET-1 is regulated by post-transcriptional mechanisms. Regulatory elements modulating mRNA half-life are often found within 3'-untranslated regions (3'-UTR). The 1.1-kb 3'-UTR of human ET-1 accounts for over 50% of the transcript length and features long tracts of highly conserved sequences including an AU-rich region. Some 3'-UTR AU-rich elements (AREs) play important regulatory roles in cytokine and proto-oncogene expression by influencing half-life under basal conditions and in response to cellular activation. Several RNA-binding proteins with affinities for AREs have been characterized including AUF1 (hnRNPD), the ELAV family (HuR, HuB, HuC, HuD), tristetraprolin, TIA/TIAR, HSP70, and others. Although specific mechanisms directing ARE activity have not been fully elucidated, current models suggest ARE-binding proteins target specific mRNAs to cellular pathways that influence 3'-polyadenylate tail and 5'-cap metabolism.

Recent studies have revealed a functional link between AUF1, heat shock proteins and the ubiquitin-proteasome network. Proteasome inhibition by chemical inhibition or heat shock was shown to stabilize a model ARE-containing mRNA whereas promotion of cellular ubiquitination pathways was shown to accelerate ARE mRNA turnover. Studies with in vitro proteasome preparations suggest that the proteasome itself may possess ARE-specific RNA destabilizing activity. The ARE-binding protein AUF1 has been linked to the ubiquitin-proteasome pathway. AUF1 mRNA destabilizing activity has been positively correlated with its level of polyubiquitination and has been shown to interact with a member of the E2 ubiquitin-conjugating protein family. Furthermore, under conditions of cellular heat shock AUF1 associates with heat shock protein 70 (HSP70), which itself possesses ARE binding activity.

The ET-1 transcript is constitutively destabilized by its 3'-UTR through two destabilizing elements, DE1 and DE2. DE1 functions through a conserved ARE by the AUF1-proteasome pathway and is regulated by the heat shock pathway.^[9]

References

^ Agapitov AV, Haynes WG; Haynes (March 2002). "Role of endothelin in cardiovascular disease". J Renin Angiotensin Aldosterone Syst. 3 (1): 1–15. PMID 11984741. doi:10.3317/jraas.2002.001.
^ Schinelli S (2006). "Pharmacology and physiopathology of the brain endothelin system: an overview". Curr. Med. Chem. 13 (6): 627–38. PMID 16529555. doi:10.2174/092986706776055652.
^ ^a ^b Microcirculation (2nd ed.). Amsterdam: Elsevier/Academic Press. 2008. pp. 305–307. ISBN 9780123745309. |first1= missing |last1= in Authors list (help)
^ Medical physiology a cellular and molecular approach (2nd ed., International ed.). Philadelphia, PA: Saunders/Elsevier. 2009. p. 480. ISBN 9781437720174. |first1= missing |last1= in Authors list (help)
^ Modern pharmacology with clinical applications (6th ed.). Philadelphia: Lippincott Williams & Wilkins. 2004. p. 215. ISBN 0781737621. |first1= missing |last1= in Authors list (help)
^ Bagnato A, Rosanò L; Rosanò (2008). "The endothelin axis in cancer". Int. J. Biochem. Cell Biol. 40 (8): 1443–51. PMID 18325824. doi:10.1016/j.biocel.2008.01.022.
^ Macdonald RL, Pluta RM, Zhang JH; Pluta; Zhang (May 2007). "Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution". Nat Clin Pract Neurol. 3 (5): 256–63. PMID 17479073. doi:10.1038/ncpneuro0490.
^ Hasue F, Kuwaki T, Kisanuki YY, Yanagisawa M, Moriya H, Fukuda Y, Shimoyama M; Kuwaki; Kisanuki; Yanagisawa; Moriya; Fukuda; Shimoyama (2005). "Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice". Neuroscience. 130 (2): 349–58. PMID 15664691. doi:10.1016/j.neuroscience.2004.09.036.
^ Mawji IA, Robb GB, Tai SC, Marsden PA; Robb; Tai; Marsden (March 2004). "Role of the 3'-untranslated region of human endothelin-1 in vascular endothelial cells. Contribution to transcript lability and the cellular heat shock response". J. Biol. Chem. 279 (10): 8655–67. PMID 14660616. doi:10.1074/jbc.M312190200.

External links

Historical background and discovery of endothelin
The International Conferences on Endothelin (Est. 1988)
Endothelin science (Actelion Pharmaceuticals)
Endothelins at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 駆出率低下を伴う心不全におけるエンドセリンの役割 role of endothelin in heart failure with reduced ejection fraction
2. エンドセリンと腎臓 endothelin and the kidney
3. 成人における肺高血圧症の治療 treatment of pulmonary hypertension in adults
4. 肺高血圧症の病因 pathogenesis of pulmonary hypertension
5. 心不全の病態生理：神経体液性の適応 pathophysiology of heart failure neurohumoral adaptations

English Journal

Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.

Rudovich N1, Pivovarova O, Bernigau W, Sparwasser A, Tacke C, Murahovshi V, Mertes G, Birkenfeld AL, Bergmann A, Weickert MO, Pfeiffer AF.
Minerva endocrinologica.Minerva Endocrinol.2016 Dec;41(4):456-68. Epub 2016 Mar 23.
BACKGROUND: Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic In
PMID 27007919

In Vitro Effects of Hollow Gold Nanoshells on Human Aortic Endothelial Cells.

Gu C1, Wu H2, Ge G1,2, Li X1, Guo Z3, Bian Z1, Xu J2, Lu H4, Chen X5, Yang D6.
Nanoscale research letters.Nanoscale Res Lett.2016 Dec;11(1):397. doi: 10.1186/s11671-016-1620-5. Epub 2016 Sep 13.
Gold nanoparticles are emerging as promising biomedical tools due to their unique nanoscale characteristics. Our purpose was to synthesize a hollow-shaped gold nanoparticle and to investigate its effect on human aortic endothelial cells (HAECs) in vitro. Hollow gold nanoshells with average 35-nm dia
PMID 27624340

Cardioprotective actions of curcumin on the pathogenic NFAT/COX-2/prostaglandin E2 pathway induced during Trypanosoma cruzi infection.

Hernández M1, Wicz S1, Corral RS2.
Phytomedicine : international journal of phytotherapy and phytopharmacology.Phytomedicine.2016 Nov 15;23(12):1392-1400. doi: 10.1016/j.phymed.2016.06.017. Epub 2016 Jun 29.
BACKGROUND: Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca2+/NFAT cascade in cardiomyocyte
PMID 27765359

Japanese Journal

Antihypertensive effects of Ocimum basilicum L. (OBL) on blood pressure in renovascular hypertensive rats

UMAR Anwar,IMAM Guzelnur,YIMIN Wuliya,KERIM Parht,TOHTI Ibadet,BERKE Benedicte,MOORE Nicholas
Hypertension research : clinical and experimental : official journal of the Japanese Society of Hypertension 33(7), 727-730, 2010-07-01
NAID 10026520449

Influence of Regular Exercise on Arterial Stiffness and Endothelium

MAEDA Seiji
Advances in exercise and sports physiology 15(4), 115-119, 2010-02
… We have focused on endothelium-derived vasoactive factors such as endothelin-1 (ET-1) and nitric oxide (NO). … ET-1 exerts potent vasoconstrictor and proliferative effects in vascular smooth muscle cells, while NO has a potent vasodilator effect and anti-athero-sclerotic properties. … ET-1 and NO have been reported to be affected by regular exercise. …
NAID 110007592905

「エンドセリン1」

Endothelin 1
Identifiers
Symbol	EDN1
Entrez	1906
HUGO	3176
OMIM	131240
RefSeq	NM_001955
UniProt	P05305
Other data
Locus	Chr. 6 p23-p24

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Endothelin family
Identifiers
Symbol	Endothelin
Pfam	PF00322
InterPro	IPR001928
PROSITE	PDOC00243
SCOP	1edp
SUPERFAMILY	1edp
OPM superfamily	156
OPM protein	3cmh
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

英: endothelin-1 ET-1
関: エンドセリン

主に血管内皮が産生する血管収縮物質

「エンドセリン-1」

　　[★]

英: endothelin-1、ET-1
関: エンドセリン1

[pmid11984741-1] Agapitov AV, Haynes WG; Haynes (March 2002). "Role of endothelin in cardiovascular disease". J Renin Angiotensin Aldosterone Syst. 3 (1): 1–15. PMID 11984741. doi:10.3317/jraas.2002.001.

[pmid16529555-2] Schinelli S (2006). "Pharmacology and physiopathology of the brain endothelin system: an overview". Curr. Med. Chem. 13 (6): 627–38. PMID 16529555. doi:10.2174/092986706776055652.

[mc-3] Microcirculation (2nd ed.). Amsterdam: Elsevier/Academic Press. 2008. pp. 305–307. ISBN 9780123745309. |first1= missing |last1= in Authors list (help)

[boron-4] Medical physiology a cellular and molecular approach (2nd ed., International ed.). Philadelphia, PA: Saunders/Elsevier. 2009. p. 480. ISBN 9781437720174. |first1= missing |last1= in Authors list (help)

[craig-5] Modern pharmacology with clinical applications (6th ed.). Philadelphia: Lippincott Williams & Wilkins. 2004. p. 215. ISBN 0781737621. |first1= missing |last1= in Authors list (help)

[pmid18325824-6] Bagnato A, Rosanò L; Rosanò (2008). "The endothelin axis in cancer". Int. J. Biochem. Cell Biol. 40 (8): 1443–51. PMID 18325824. doi:10.1016/j.biocel.2008.01.022.

[pmid17479073-7] Macdonald RL, Pluta RM, Zhang JH; Pluta; Zhang (May 2007). "Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution". Nat Clin Pract Neurol. 3 (5): 256–63. PMID 17479073. doi:10.1038/ncpneuro0490.

[pmid15664691-8] Hasue F, Kuwaki T, Kisanuki YY, Yanagisawa M, Moriya H, Fukuda Y, Shimoyama M; Kuwaki; Kisanuki; Yanagisawa; Moriya; Fukuda; Shimoyama (2005). "Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice". Neuroscience. 130 (2): 349–58. PMID 15664691. doi:10.1016/j.neuroscience.2004.09.036.

[pmid14660616-9] Mawji IA, Robb GB, Tai SC, Marsden PA; Robb; Tai; Marsden (March 2004). "Role of the 3'-untranslated region of human endothelin-1 in vascular endothelial cells. Contribution to transcript lability and the cellular heat shock response". J. Biol. Chem. 279 (10): 8655–67. PMID 14660616. doi:10.1074/jbc.M312190200.

v t e Intercellular signaling peptides and proteins / ligands
Growth factors	Epidermal growth factor Fibroblast growth factor Nerve growth factor Platelet-derived growth factor Transforming growth factor beta superfamily Vascular endothelial growth factor
Ephrin	EFNA1 EFNA2 EFNA3 EFNA4 EFNA5 EFNB1 EFNB2 EFNB3
Other	Adipokine Agouti signaling protein Agouti-related protein Angiogenic protein CCN intercellular signaling protein Cysteine-rich protein 61 Connective tissue growth factor Nephroblastoma overexpressed protein Cytokine Endothelin EDN1 EDN2 EDN3 Hedgehog protein Interferon Kinin Parathyroid hormone-related protein Semaphorin Somatomedin Tolloid-like metalloproteinase Tumor necrosis factor Wnt protein
see also extracellular ligand disorders

匿名

検索

案内

案内

endothelin-1