Extracellular Phosphate, Inflammation and Cytotoxicity
Extracellular Phosphate, Inflammation and Cytotoxicity
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细胞外磷酸盐、炎症和细胞毒性
DOI：
10.1007/978-3-030-91623-7_3
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Razzaque Mohammed S.
中科院分区：
文献类型：
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作者：
Michigami Toshimi;Yamazaki Miwa;Razzaque Mohammed S.
磷是一种必需的营养素，在各种生物过程中起着至关重要的作用，包括细胞膜完整性、核酸合成、能量代谢、细胞内信号传导和硬组织矿化。因此，磷平衡的控制在所有生物体中都是至关重要的，而成纤维细胞生长因子23（FGF 23）-αKlotho系统是维持哺乳动物体内磷酸盐稳态的核心。虽然磷酸盐是基本细胞功能不可或缺的，但它的过度保留是有毒的，可以影响几乎所有器官系统的功能。在人类患者中，高磷酸盐血症与发病率和死亡率的增加有关。此外，通过破坏FGF 23-αKlotho系统产生的高磷酸盐血症小鼠模型表现出广泛的组织损伤、过早衰老和寿命短。使用细胞和动物模型的实验研究表明，磷酸盐升高的细胞毒性和炎症效应部分由异常细胞信号传导和氧化应激介导。本文综述了我们目前对磷酸盐毒性的认识。
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.