权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Antioxidant defence in adrenocortical cells

肾上腺皮质细胞的抗氧化防御

基本信息

批准号：
MR/K020455/1
负责人：
Louise Metherell
金额：
$ 50.01万
依托单位：
Queen Mary University of London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FK020455%2F1
关键词：
Antioxidant defence adrenocortical cells

项目摘要

Oxidative stress (OS) is involved in many human disease states including neurodegenerative diseases, cancer, stroke, diabetes and heart disease. We study patients with a rare disease called Familial Glucocorticoid Deficiency (FGD) in which the body fails to produce a glucocorticoid called cortisol. Patients with this disease do not have a mechanism to cope with stress. If their body becomes stressed, for example by illness, their blood sugar levels drop, they become liable to infections and they may die if untreated. ACTH, acting through its receptor, is the hormone that is produced in response to stress and it causes the cells of the adrenal gland to produce cortisol. We have previously found defects in three genes in this pathway that cause FGD. More recently we have discovered that defects in four genes usually associated with a cells defence against oxidative stress, can also cause the disease. Exactly how OS prevents cortisol secretion is not fully understood and we believe that other genes may also be involved. This project aims to discover the mechanism by which OS affects the cells of the adrenal to prevent them making cortisol. We also hope to find other genes in this pathway by studying the genetic make-up of FGD patients. If we can discover how the OS causes its effect then this might give us clues to the mechanism in other diseases like those listed above and it may then be possible to design drugs to reduce it.

氧化应激（OS）参与许多人类疾病状态，包括神经退行性疾病、癌症、中风、糖尿病和心脏病。我们研究了一种罕见的疾病，称为家族性糖皮质激素缺乏症（FGD）的患者，其中身体无法产生一种称为皮质醇的糖皮质激素。患有这种疾病的患者没有科普压力的机制。如果他们的身体变得紧张，例如疾病，他们的血糖水平下降，他们变得容易感染，如果不治疗，他们可能会死亡。促肾上腺皮质激素通过其受体起作用，是一种在压力下产生的激素，它使肾上腺细胞产生皮质醇。我们以前已经发现了导致FGD的这一途径中的三个基因的缺陷。最近，我们发现通常与细胞防御氧化应激相关的四种基因的缺陷也会导致这种疾病。OS究竟如何阻止皮质醇分泌尚未完全了解，我们相信其他基因也可能参与其中。本项目旨在发现OS影响肾上腺细胞以阻止它们产生皮质醇的机制。我们还希望通过研究FGD患者的遗传组成来找到这一途径中的其他基因。如果我们能发现OS是如何引起其效应的，那么这可能会给我们提供线索，了解其他疾病的机制，比如上面列出的那些疾病，然后就有可能设计药物来减少它。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Can Digenic, Tri-Allelic Inheritance of Variants in STAR and CYP11A1 Give Rise to Primary Adrenal Insufficiency? A Case Report.

DOI：
10.3389/fendo.2022.860055
发表时间：
2022
期刊：
Frontiers in endocrinology
影响因子：
5.2
作者：
Ali N;Maharaj AV;Buonocore F;Achermann JC;Metherell LA
通讯作者：
Metherell LA

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

DOI：
10.1038/s41588-021-00906-y
发表时间：
2021-09
期刊：
NATURE GENETICS
影响因子：
30.8
作者：
Zhou, Junhua;Azizan, Elena A. B.;Cabrera, Claudia P.;Fernandes-Rosa, Fabio L.;Boulkroun, Sheerazed;Argentesi, Giulia;Cottrell, Emily;Amar, Laurence;Wu, Xilin;O'Toole, Sam;Goodchild, Emily;Marker, Alison;Senanayake, Russell;Garg, Sumedha;Akerstrom, Tobias;Backman, Samuel;Jordan, Suzanne;Polubothu, Satyamaanasa;Berney, Daniel M.;Gluck, Anna;Lines, Kate E.;Thakker, Rajesh V.;Tuthill, Antoinette;Joyce, Caroline;Kaski, Juan Pablo;Karet Frankl, Fiona E.;Metherell, Lou A.;Teo, Ada E. D.;Gurnell, Mark;Parvanta, Laila;Drake, William M.;Wozniak, Eva;Klinzing, David;Kuan, Jyn Ling;Tiang, Zenia;Gomez Sanchez, Celso E.;Hellman, Per;Foo, Roger S. Y.;Mein, Charles A.;Kinsler, Veronica A.;Bjorklund, Peyman;Storr, Helen L.;Zennaro, Maria-Christina;Brown, Morris J.
通讯作者：
Brown, Morris J.

Somatic Mutations of GNA11 and GNAQ in CTNNB1-Mutant Aldosterone-Producing Adenomas Increases Aldosterone and Aldosterone Synthase (CYP11B2)

CTNNB1 突变型醛固酮腺瘤中 GNA11 和 GNAQ 的体细胞突变会增加醛固酮和醛固酮合酶 (CYP11B2)