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翻译控制肿瘤蛋白(TCTP)在小鼠模型高血压及相关疾病发生发展中的作用

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models.

作者信息

Maeng Jeehye, Lee Kyunglim

机构信息

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea.

出版信息

Biomedicines. 2022 Oct 27;10(11):2722. doi: 10.3390/biomedicines10112722.

Abstract

Translationally controlled tumor protein (TCTP) is a multifunctional protein that plays a wide variety of physiological and pathological roles, including as a cytoplasmic repressor of Na,K-ATPase, an enzyme pivotal in maintaining Na and K ion gradients across the plasma membrane, by binding to and inhibiting Na,K-ATPase. Studies with transgenic mice overexpressing TCTP (TCTP-TG) revealed the pathophysiological significance of TCTP in the development of systemic arterial hypertension. Overexpression of TCTP and inhibition of Na,K-ATPase result in the elevation of cytoplasmic Ca levels, which increases the vascular contractility in the mice, leading to hypertension. Furthermore, studies using an animal model constructed by multiple mating of TCTP-TG with apolipoprotein E knockout mice (ApoE KO) indicated that TCTP-induced hypertension facilitates the severity of atherosclerotic lesions in vivo. This review attempts to discuss the mechanisms underlying TCTP-induced hypertension and related diseases gleaned from studies using genetically altered animal models and the potential of TCTP as a target in the therapy of hypertension-related pathological conditions.

摘要

翻译调控肿瘤蛋白(TCTP)是一种多功能蛋白,发挥着广泛的生理和病理作用,包括作为钠钾ATP酶的胞质抑制剂,钠钾ATP酶是维持质膜两侧钠钾离子梯度的关键酶,TCTP通过与钠钾ATP酶结合并抑制其活性来发挥作用。对过表达TCTP的转基因小鼠(TCTP-TG)的研究揭示了TCTP在系统性动脉高血压发生发展中的病理生理意义。TCTP的过表达和钠钾ATP酶的抑制导致细胞质钙水平升高,这增加了小鼠的血管收缩性,从而导致高血压。此外,使用通过将TCTP-TG与载脂蛋白E基因敲除小鼠(ApoE KO)多次交配构建的动物模型进行的研究表明,TCTP诱导的高血压在体内会加剧动脉粥样硬化病变的严重程度。本综述试图讨论从使用基因改变动物模型的研究中得出的TCTP诱导高血压及相关疾病的潜在机制,以及TCTP作为高血压相关病理状况治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/023c/9687121/a4a734050946/biomedicines-10-02722-g001.jpg

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