Bertram Catharina, Hass Ralf
Department of Gynecology (OE 6411), Medical School Hannover, D-30625 Hannover, Germany.
Biol Chem. 2008 Mar;389(3):211-20. doi: 10.1515/BC.2008.031.
Oxidative stress in cells and tissues can occur during pathophysiological developments, e.g., during inflammatory and allergic diseases or during ischemic or toxic and hyperglycemic conditions via the generation of reactive oxygen species (ROS). Moreover, ROS can be generated by radiation (UV, X-rays) and pharmacologically, e.g., by anthracyclins as chemotherapeutic compounds for treatment of a variety of tumors to induce 'stress or aberrant signaling-inducing senescence' (STASIS). Although STASIS is distinguished from intracellular replicative senescence, a variety of cellular mechanisms appear similar in both aging pathways. It is generally accepted that oxidative stress and ROS eventually cause DNA damage, whereby insufficient cellular repair mechanisms may contribute to premature aging and apoptosis. Conversely, ROS-induced imbalances of the signaling pathways for metabolic protein turnover may also result in opposite effects to recruit malfunctioning aberrant proteins and compounds that trigger tumorigenic processes. Consequently, DNA damage plays a role in the development of carcinogenesis, but is also associated with an aging process in cells and organisms.
细胞和组织中的氧化应激可在病理生理发展过程中发生，例如在炎症和过敏性疾病期间，或在缺血、中毒和高血糖情况下，通过活性氧（ROS）的产生而发生。此外，ROS可由辐射（紫外线、X射线）产生，也可通过药理学方式产生，例如通过蒽环类药物作为治疗多种肿瘤的化疗化合物，以诱导“应激或异常信号诱导衰老”（STASIS）。尽管STASIS与细胞内复制性衰老不同，但在这两种衰老途径中，多种细胞机制似乎相似。人们普遍认为，氧化应激和ROS最终会导致DNA损伤，而细胞修复机制不足可能会导致早衰和细胞凋亡。相反，ROS诱导的代谢蛋白周转信号通路失衡也可能产生相反的效果，即募集引发肿瘤发生过程的功能异常的异常蛋白和化合物。因此，DNA损伤在致癌作用的发展中起作用，但也与细胞和生物体的衰老过程有关。
