Roti Roti Joseph L
Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Int J Hyperthermia. 2008 Feb;24(1):3-15. doi: 10.1080/02656730701769841.
The goal of this review is to provide a brief introduction to the effects of hyperthermia on cellular structures and physiology. The review focuses on the effects of hyperthermia thought to contribute to the enhancement of cancer therapy namely the mechanisms of cell killing and the sensitization of cells to ionizing radiation or chemotherapeutic agents. Specifically the review addresses four topics: hyperthermia induced cell killing, mathematical models of cell killing, mechanisms of thermal effects in the hyperthermia temperature range and effects on proteins that contribute to resistance to other stresses, i.e., DNA damage. Hyperthermia has significant effects on proteins including unfolding, exposing hydrophobic groups, and aggregation with proteins not directly altered by hyperthermia. Protein aggregation has effects throughout the cell but has a significant impact within the nucleus. Changes in the associations of nuclear proteins particularly those involved in DNA replication cause the stalling of DNA replication forks and lead to the induction of DNA damage such as double strand breaks. It has long been recognized that heat has effects on plasma membrane protein distribution alters the permeability of plasma membranes resulting in a calcium spike and disrupts the mitochondrial membrane potential resulting in the change in the redox status of cells. These effects contribute to the protein unfolding effects of hyperthermia and contribute to effects observed in the nucleus. Thus heat effects on multiple cellular targets can be integrated through global effects on protein folding to affect specific end points such as cell killing and sensitization to additional stresses.
本综述的目的是简要介绍热疗对细胞结构和生理的影响。该综述聚焦于热疗被认为有助于增强癌症治疗效果的那些影响，即细胞杀伤机制以及细胞对电离辐射或化疗药物的致敏作用。具体而言，该综述探讨了四个主题：热疗诱导的细胞杀伤、细胞杀伤的数学模型、热疗温度范围内的热效应机制以及对有助于抵抗其他应激（即DNA损伤）的蛋白质的影响。热疗对蛋白质有显著影响，包括使其展开、暴露疏水基团以及与未直接受热疗改变的蛋白质聚集。蛋白质聚集在整个细胞内都有影响，但在细胞核内影响尤为显著。核蛋白关联的变化，特别是那些参与DNA复制的核蛋白，会导致DNA复制叉停滞，并引发DNA损伤，如双链断裂。长期以来人们一直认识到，热会影响质膜蛋白分布，改变质膜通透性，导致钙峰出现，并破坏线粒体膜电位，从而导致细胞氧化还原状态改变。这些效应促成了热疗对蛋白质的展开作用，并导致在细胞核中观察到的效应。因此，热对多个细胞靶点的影响可以通过对蛋白质折叠的全局影响进行整合，以影响特定的终点，如细胞杀伤和对其他应激的致敏作用。
