Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Izumi, Osaka, Japan.
Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, PA, USA.
Adv Exp Med Biol. 2022;1362:15-25. doi: 10.1007/978-3-030-91623-7_3.
Phosphorus is an essential nutrient that plays a crucial role in various biological processes, including cell membrane integrity, synthesis of nucleic acids, energy metabolism, intracellular signaling, and hard tissue mineralization. Therefore, the control of phosphorus balance is critical in all living organisms, and the fibroblast growth factor 23 (FGF23)-αKlotho system is central to maintain phosphate homeostasis in mammals. Although phosphate is indispensable for basic cellular functions, its excessive retention is toxic and can affect almost all organ systems' functionality. In human patients, hyperphosphatemia has been implicated in an increase in morbidity and mortality. Also, mouse models with hyperphosphatemia generated by disruption of the FGF23-αKlotho system exhibit extensive tissue damage, premature aging, and a short lifespan. Experimental studies using cell and animal models suggest that cytotoxic and inflammatory effects of elevated phosphate are partly mediated by abnormal cell signaling and oxidative stress. This review provides an overview of our current understanding regarding the toxicity of phosphate.
磷是一种必需的营养物质，在各种生物过程中发挥着关键作用，包括细胞膜完整性、核酸合成、能量代谢、细胞内信号转导和硬组织矿化。因此，磷平衡的控制在所有生物体中都至关重要，而成纤维细胞生长因子 23（FGF23）-αKlotho 系统是维持哺乳动物磷酸盐稳态的核心。尽管磷酸盐对基本细胞功能是不可或缺的，但它的过度蓄积是有毒的，并会影响几乎所有器官系统的功能。在人类患者中，高磷血症与发病率和死亡率的增加有关。此外，通过破坏 FGF23-αKlotho 系统生成的高磷血症的小鼠模型表现出广泛的组织损伤、早衰和寿命缩短。使用细胞和动物模型的实验研究表明，升高的磷酸盐的细胞毒性和炎症作用部分是由异常细胞信号和氧化应激介导的。本综述提供了我们目前对磷酸盐毒性的理解概述。
