Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Piazza Lauro De Bosis 15, 00135 Rome, Italy.
Unit of Biology, Genetics and Biochemistry, Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Piazza Lauro De Bosis 15, 00135 Rome, Italy.
Free Radic Biol Med. 2016 Sep;98:46-55. doi: 10.1016/j.freeradbiomed.2016.03.028. Epub 2016 Mar 26.
Cells have evolved multiple and sophisticated stress response mechanisms aiming to prevent macromolecular (including proteins, lipids, and nucleic acids) damage and to maintain or re-establish cellular homeostasis. Heat shock proteins (HSPs) are among the most highly conserved, ubiquitous, and abundant proteins in all organisms. Originally discovered more than 50 years ago through heat shock stress, they display multiple, remarkable roles inside and outside cells under a variety of stresses, including also oxidative stress and radiation, recognizing unfolded or misfolded proteins and facilitating their restructuring. Exercise consists in a combination of physiological stresses, such as metabolic disturbances, changes in circulating levels of hormones, increased temperature, induction of mild to severe inflammatory state, increased production of reactive oxygen and nitrogen species (ROS and RNS). As a consequence, exercise is one of the main stimuli associated with a robust increase in different HSPs in several tissues, which appears to be also fundamental in facilitating the cellular remodeling processes related to the training regime. Among all factors involved in the exercise-related modulation of HSPs level, the ROS production in the contracting muscle or in other tissues represents one of the most attracting, but still under discussion, mechanism. Following exhaustive or damaging muscle exercise, major oxidative damage to proteins and lipids is likely involved in HSP expression, together with mechanically induced damage to muscle proteins and the inflammatory response occurring several days into the recovery period. Instead, the transient and reversible oxidation of proteins by physiological concentrations of ROS seems to be involved in the activation of stress response following non-damaging muscle exercise. This review aims to provide a critical update on the role of HSPs response in exercise-induced adaptation or damage in humans, focusing on experimental results where the link between redox homeostasis and HSPs expression by exercise has been addressed. Further, with the support of in vivo and in vitro studies, we discuss the putative molecular mechanisms underlying the ROS-mediated modulation of HSP expression and/or activity during exercise.
细胞已经进化出多种复杂的应激反应机制，旨在防止大分子（包括蛋白质、脂质和核酸）损伤，并维持或重新建立细胞内稳态。热休克蛋白（HSPs）是所有生物中最保守、普遍和丰富的蛋白质之一。它们最初是在 50 多年前通过热休克应激发现的，在各种应激下，包括氧化应激和辐射，在细胞内外具有多种显著作用，识别未折叠或错误折叠的蛋白质并促进其重折叠。运动是一种生理应激的组合，例如代谢紊乱、激素循环水平的变化、体温升高、诱导轻度至重度炎症状态、活性氧和氮物种（ROS 和 RNS）产生增加。因此，运动是与几种组织中不同 HSP 大量增加相关的主要刺激之一，这似乎对于促进与训练方案相关的细胞重塑过程也很重要。在与运动相关的 HSP 水平调节中涉及的所有因素中，收缩肌肉或其他组织中的 ROS 产生是最吸引人的机制之一，但仍在讨论中。在剧烈或损伤性肌肉运动后，蛋白质和脂质的主要氧化损伤可能与 HSP 表达有关，同时还涉及肌肉蛋白的机械损伤和恢复期间数天发生的炎症反应。相反，生理浓度的 ROS 对蛋白质的短暂和可逆氧化似乎参与了非损伤性肌肉运动后的应激反应激活。本综述旨在提供关于 HSP 反应在人类运动诱导适应或损伤中的作用的最新批判性评价，重点介绍了已经解决了氧化还原平衡与运动诱导的 HSP 表达之间联系的实验结果。此外，我们还在体内和体外研究的支持下，讨论了 ROS 介导的 HSP 表达和/或活性调节在运动期间的潜在分子机制。
