Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Arch Biochem Biophys. 2023 Sep 1;745:109718. doi: 10.1016/j.abb.2023.109718. Epub 2023 Aug 12.
Current progress in biology and medical science is based on the observation at the level of nanometers via electron microscopy and computation. Of note, the size of most cells in higher species exists in a limited range from 5 to 50 μm. Recently, it was demonstrated that endogenous extracellular nanoparticles play a role in communication among various cellular types in a variety of contexts. Among them, exosomes in serum have been established as biomarkers for human diseases by analyzing the cargo molecules. No life on the earth can survive without iron. However, excess iron can be a risk for carcinogenesis in rodents and humans. Nano-sized molecules may cause unexpected bioeffects, including carcinogenesis, which is a process to establish cellular iron addiction with ferroptosis-resistance. Asbestos and carbon nanotubes are the typical examples, leading to carcinogenesis by the alteration of iron metabolism. Recently, we found that CD63, one of the representative markers of exosomes, is under the regulation of iron-responsive element/iron-regulatory protein system. This is a safe strategy to share excess iron in the form of holo-ferritin between iron-sufficient and -deficient cells. On the other hand, damaged cells may secrete holo-ferritin-loaded exosomes as in the case of macrophages in ferroptosis after asbestos exposure. These holo-ferritin-loaded exosomes can cause mutagenic DNA damage in the recipient mesothelial cells. Thus, there is an iron link between exogenous and endogenous nanoparticles, which requires further investigation for better understanding and the future applications.
当前生物学和医学科学的进展是基于电子显微镜和计算在纳米级水平的观察。值得注意的是，大多数高等生物的细胞大小存在于一个有限的范围内，从 5 到 50μm。最近，研究表明内源性细胞外纳米颗粒在各种细胞类型之间的通讯中发挥作用，在各种情况下都是如此。其中，血清中的外泌体通过分析货物分子已被确立为人类疾病的生物标志物。没有铁，地球上的任何生命都无法生存。然而，过量的铁可能会增加啮齿动物和人类致癌的风险。纳米级分子可能会引起意想不到的生物效应，包括致癌作用，这是一个建立细胞铁依赖性和铁死亡抗性的过程。石棉和碳纳米管就是典型的例子，通过改变铁代谢导致致癌作用。最近，我们发现外泌体的代表性标志物之一 CD63 受铁反应元件/铁调节蛋白系统的调节。这是一种在铁充足和铁缺乏细胞之间以铁蛋白的形式共享多余铁的安全策略。另一方面，受损细胞可能会分泌负载铁蛋白的外泌体，就像暴露于石棉后铁死亡的巨噬细胞一样。这些负载铁蛋白的外泌体可以在受体间皮细胞中引起致突变的 DNA 损伤。因此，外源性和内源性纳米颗粒之间存在铁的联系，需要进一步研究以更好地理解和未来应用。
