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[Her2/neu转基因小鼠神经内分泌系统中凋亡标志物蛋白表达的年龄依赖性特点]

[Age-dependent peculiarities of apoptotic marker proteins expression in the neuroendocrine system of Her2/neu transgenic mice].

作者信息

Bazhanova E D, Molodtsov V N, Popovich I G, Anisimov V N

出版信息

Morfologiia. 2007;131(3):22-5.

Abstract

The aim of our work was to study the expression of apoptotic signaling proteins and its relation to apoptosis level in neuroendocrine system of HER2/neu transgenic mice in aging. SHR mice served as controls. Bcl-2, Mcl-1, p53 and caspase-8 were demonstrated by immunohistochemistry in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and relative content of apoptotic neurosecretory cells was determined. It was demonstrated that apoptosis regulation in different nuclei in old SHR mice was mediated by various signaling pathways: in SON, p53-independent cascade was activated, while in PVN it was p53-dependent. Overexpression of HER2/neu was shown to protect against the age-related apoptosis activation in neurosecretory centers. HER2/neu suppressed the synthesis of proapoptotic protein p53, causing the reduction of caspase-8 expression, that resulted in the increased survival of neurosecretory cells in aging.

摘要

我们研究的目的是探讨衰老过程中HER2/neu转基因小鼠神经内分泌系统中凋亡信号蛋白的表达及其与凋亡水平的关系。以SHR小鼠作为对照。通过免疫组织化学方法检测视上核(SON)和室旁核(PVN)中Bcl-2、Mcl-1、p53和caspase-8的表达,并测定凋亡神经分泌细胞的相对含量。结果表明,老年SHR小鼠不同核团中的凋亡调控由多种信号通路介导:在视上核中,激活的是不依赖p53的级联反应,而在室旁核中则是依赖p53的。研究显示,HER2/neu的过表达可防止神经分泌中枢中与年龄相关的凋亡激活。HER2/neu抑制促凋亡蛋白p53的合成,导致caspase-8表达降低,从而使衰老过程中神经分泌细胞的存活率增加。

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