Schirrmacher Volker
Immune-Oncological Center Cologne (IOZK), D-50674 Cologne, Germany.
Biomedicines. 2021 Mar 13;9(3):293. doi: 10.3390/biomedicines9030293.
A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness. Physical stress can be exerted through heat, radiation, or physical exercise. Chemical stressors include reactive species from oxygen (ROS), nitrogen (RNS), and carbon (RCS), carcinogens, elements, such as lithium (Li) and silicon (Si), and metals, such as silver (Ag), cadmium (Cd), and lead (Pb). Anthropogenic chemicals are agrochemicals (phytotoxins, herbicides), industrial chemicals, and pharmaceuticals. Biochemical stress can be exerted through toxins, medical drugs (e.g., cytostatics, psychopharmaceuticals, non-steroidal inhibitors of inflammation), and through fasting (dietary restriction). Key-lock interactions between enzymes and substrates, antigens and antibodies, antigen-presenting cells, and cognate T cells are the basics of biology, biochemistry, and immunology. Their rules do not obey linear dose-response relationships. The review provides examples of biologic stressors: oncolytic viruses (e.g., immuno-virotherapy of cancer) and hormones (e.g., melatonin, stress hormones). Molecular mechanisms of cellular stress adaptation involve the protein quality control system (PQS) and homeostasis of proteasome, endoplasmic reticulum, and mitochondria. Important components are transcription factors (e.g., Nrf2), micro-RNAs, heat shock proteins, ionic calcium, and enzymes (e.g., glutathion redox enzymes, DNA methyltransferases, and DNA repair enzymes). Cellular growth control, intercellular communication, and resistance to stress from microbial infections involve growth factors, cytokines, chemokines, interferons, and their respective receptors. The effects of hormesis during evolution are multifarious: cell protection and survival, evolutionary flexibility, and epigenetic memory. According to the hormesis theory, this is true for the entire biosphere, e.g., archaia, bacteria, fungi, plants, and the animal kingdoms.
根据兴奋效应理论，应激源的剂量-反应关系的特点是低剂量刺激和高剂量抑制。它是非线性的，存在低剂量最佳值。细胞的应激反应会带来适应性的活力和健康状态。物理应激可通过热、辐射或体育锻炼施加。化学应激源包括来自氧（ROS）、氮（RNS）和碳（RCS）的活性物质、致癌物、元素（如锂（Li）和硅（Si））以及金属（如银（Ag）、镉（Cd）和铅（Pb））。人为化学物质包括农用化学品（植物毒素、除草剂）、工业化学品和药物。生化应激可通过毒素、药物（如细胞抑制剂、精神药物、非甾体抗炎药）以及禁食（饮食限制）施加。酶与底物、抗原与抗体、抗原呈递细胞和同源T细胞之间的锁钥相互作用是生物学、生物化学和免疫学的基础。它们的规则不遵循线性剂量-反应关系。本综述提供了生物应激源的例子：溶瘤病毒（如癌症的免疫病毒疗法）和激素（如褪黑素、应激激素）。细胞应激适应的分子机制涉及蛋白质质量控制系统（PQS）以及蛋白酶体、内质网和线粒体的稳态。重要组成部分包括转录因子（如Nrf2）、微小RNA、热休克蛋白、离子钙和酶（如谷胱甘肽氧化还原酶、DNA甲基转移酶和DNA修复酶）。细胞生长控制、细胞间通讯以及对微生物感染应激的抗性涉及生长因子、细胞因子、趋化因子、干扰素及其各自的受体。兴奋效应在进化过程中的作用是多方面的：细胞保护与存活、进化灵活性和表观遗传记忆。根据兴奋效应理论，这适用于整个生物圈，如古细菌、细菌、真菌、植物和动物界。
