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抑制素:基于性别的代谢和免疫疾病新疗法的假设靶点。

Prohibitin: A hypothetical target for sex-based new therapeutics for metabolic and immune diseases.

机构信息

1 Department of Internal Medicine, University of Manitoba, Manitoba R3A1R9, Canada.

2 Department of Physiology & Pathophysiology, University of Manitoba, Manitoba R3E0J9, Canada.

出版信息

Exp Biol Med (Maywood). 2019 Feb;244(2):157-170. doi: 10.1177/1535370219828362. Epub 2019 Feb 4.

Abstract

Traditional sex-related biases in research are now obsolete, and it is important to identify the sex of humans, animals, and even cells in research protocols, due to the role of sex as a fundamental facet of biology, predisposition to disease, and response to therapy. Genetic sex, epigenetics and hormonal regulations, generate sex-dimorphisms. Recent investigations acknowledge sex differences in metabolic and immune health as well as chronic diseases. Prohibitin, an evolutionarily conserved molecule, has pleotropic functions in mitochondrial housekeeping, plasma membrane signaling, and nuclear genetic transcription. Studies in adipocytes, macrophages, and transgenic mice indicate that prohibitin interacts with sex steroids and plays a role in mediating sex differences in adipose tissues and immune cell types. Prohibitin may, depending on context, modulate predisposition to chronic metabolic diseases and malignancy and, because of these attributes, could be a target for sex-based therapies of metabolic and immune-related diseases as well as cancer.

摘要

传统的与性相关的研究偏见现在已经过时了,由于性是生物学、疾病易感性和治疗反应的一个基本方面,因此在研究方案中确定人类、动物甚至细胞的性别非常重要。遗传性别、表观遗传和激素调节会产生性别二态性。最近的研究承认代谢和免疫健康以及慢性疾病存在性别差异。阻遏蛋白是一种进化上保守的分子,在线粒体管家、质膜信号和核遗传转录中具有多种功能。脂肪细胞、巨噬细胞和转基因小鼠的研究表明,阻遏蛋白与性激素相互作用,在调节脂肪组织和免疫细胞类型中的性别差异方面发挥作用。阻遏蛋白可能根据具体情况调节慢性代谢性疾病和恶性肿瘤的易感性,由于这些特性,它可能成为代谢和免疫相关疾病以及癌症的基于性别的治疗的靶点。

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本文引用的文献

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Sex Hormones in Acquired Immunity and Autoimmune Disease.性激素与获得性免疫及自身免疫性疾病
Front Immunol. 2018 Oct 4;9:2279. doi: 10.3389/fimmu.2018.02279. eCollection 2018.
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Mitochondrial damage and iron metabolic dysregulation in hepatitis C virus infection.丙型肝炎病毒感染中的线粒体损伤和铁代谢失调。
Free Radic Biol Med. 2019 Mar;133:193-199. doi: 10.1016/j.freeradbiomed.2018.09.044. Epub 2018 Sep 27.
8
Prohibitin: a potential therapeutic target in tyrosine kinase signaling.抑素:酪氨酸激酶信号转导的潜在治疗靶点。
Signal Transduct Target Ther. 2017 Dec 15;2:17059. doi: 10.1038/sigtrans.2017.59. eCollection 2017.

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