Mild heat shock at 40 °C increases levels of autophagy: Role of Nrf2

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Mélanie Grondin, Claire Chabrol, Diana A. Averill-Bates
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引用次数: 0

Abstract

The exposure to low doses of stress induces an adaptive survival response that involves the upregulation of cellular defense systems such as heat shock proteins (Hsps), anti-apoptosis proteins, and antioxidants. Exposure of cells to elevated, non-lethal temperatures (39–41 °C) is an adaptive survival response known as thermotolerance, which protects cells against subsequent lethal stress such as heat shock (>41.5 °C). However, the initiating factors in this adaptive survival response are not understood. This study aims to determine whether autophagy can be activated by heat shock at 40 °C and if this response is mediated by the transcription factor Nrf2. Thermotolerant cells, which were developed during 3 h at 40 °C, were resistant to caspase activation at 42 °C. Autophagy was activated when cells were heated from 5 to 60 min at 40 °C. Levels of acidic vesicular organelles (AVOs) and autophagy proteins Beclin-1, LC3-II/LC3-I, Atg7, Atg5, Atg12–Atg5, and p62 were increased. When Nrf2 was overexpressed or depleted in cells, levels of AVOs and autophagy proteins were higher in unstressed cells, compared to the wild type. Stress induced by mild heat shock at 40 °C further increased levels of most autophagy proteins in cells with overexpression or depletion of Nrf2. Colocalization of p62 and Keap1 occurred. When Nrf2 levels are low, activation of autophagy would likely compensate as a defense mechanism to protect cells against stress. An improved understanding of autophagy in the context of cellular responses to physiological heat shock could be useful for cancer treatment by hyperthermia and the protective role of adaptive responses against environmental stresses.

40ºC 的轻度热休克可提高自噬水平:Nrf2 的作用。
暴露于低剂量的应激会诱发一种适应性生存反应,其中涉及热休克蛋白(Hsp)、抗凋亡蛋白和抗氧化剂等细胞防御系统的上调。将细胞暴露于非致命的高温(39-41°C)是一种适应性生存反应,被称为耐热性,可保护细胞免受随后的致命应激,如热休克(>41.5°C)。然而,这种适应性生存反应的启动因素尚不清楚。本研究旨在确定自噬是否能被40°C的热休克激活,以及这种反应是否由转录因子Nrf2介导。耐热细胞在40°C条件下生长3小时,在42°C条件下对caspase激活具有抵抗力。当细胞在40°C下加热5至60分钟时,自噬被激活。酸性囊泡细胞器(AVO)和自噬蛋白Beclin-1、LC3-II/LC3-I、Atg7、Atg5、Atg12-Atg5和p62的水平均升高。与野生型相比,当细胞中的Nrf2被过表达或耗竭时,未受压细胞中的AVOs和自噬蛋白水平较高。40ºC轻度热休克诱导的应激进一步提高了Nrf2过表达或缺失细胞中大多数自噬蛋白的水平。p62和Keap1发生了共定位。当Nrf2水平较低时,自噬的激活很可能会作为一种防御机制来保护细胞免受压力。进一步了解细胞对生理性热休克的反应中的自噬现象,对通过热疗治疗癌症以及对环境压力的适应性反应的保护作用很有帮助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Stress & Chaperones
Cell Stress & Chaperones 生物-细胞生物学
CiteScore
7.60
自引率
2.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.
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