Laboratório de Bioquímica Celular, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-901, Brazil.
Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ 21941-590, Brazil.
Int J Mol Sci. 2020 Dec 6;21(23):9298. doi: 10.3390/ijms21239298.
Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-independent Pi transporter has been identified. This transporter assists in the absorption of Pi by intestinal cells and renal proximal tubule cells and in the reabsorption of Pi by osteoclasts and capillaries of the blood-brain barrier (BBB). Hyperphosphatemia is a risk factor for mineral deposition, the development of diseases such as osteoarthritis, and vascular calcifications (VCs). Na-independent Pi transporters have been identified and biochemically characterized in vascular smooth muscle cells (VSMCs), chondrocytes, and matrix vesicles, and their involvement in mineral deposition in the extracellular microenvironment has been suggested. According to the growth rate hypothesis, cancer cells require more phosphate than healthy cells due to their rapid growth rates. Recently, it was demonstrated that breast cancer cells (MDA-MB-231) respond to high Pi concentration (2 mM) by decreasing Na-dependent Pi transport activity concomitant with an increase in Na-independent (H-dependent) Pi transport. This Pi H-dependent transport has a fundamental role in the proliferation and migratory capacity of MDA-MB-231 cells. The purpose of this review is to discuss experimental findings regarding Na-independent inorganic phosphate transporters and summarize their roles in Pi homeostasis, cancers and other diseases, such as osteoarthritis, and in processes such as VC.
无机磷酸盐（Pi）是维持细胞的必需营养素。在健康的哺乳动物中，细胞外的 Pi 维持在 0.70 至 1.55mM 的狭窄浓度范围内。哺乳动物细胞依赖于 Na/Pi 协同转运蛋白来吸收 Pi，这已得到了很好的研究。然而，已经鉴定出一种新型的钠非依赖性 Pi 转运蛋白。这种转运蛋白有助于肠道细胞和肾近端小管细胞吸收 Pi，以及破骨细胞和血脑屏障（BBB）的毛细血管重吸收 Pi。高磷血症是矿物质沉积、骨关节炎等疾病发展和血管钙化（VCs）的风险因素。已经在血管平滑肌细胞（VSMCs）、软骨细胞和基质小泡中鉴定出并生化表征了非 Na 依赖性 Pi 转运蛋白，并提出了它们在细胞外微环境中矿物质沉积中的作用。根据生长速率假说，由于癌细胞的快速生长速度，它们比健康细胞需要更多的磷酸盐。最近，已经证明乳腺癌细胞（MDA-MB-231）通过降低伴随 Na 依赖性 Pi 转运活性增加的高 Pi 浓度（2mM）来响应，Na 非依赖性（H 依赖性）Pi 转运增加。这种 Pi H 依赖性转运在 MDA-MB-231 细胞的增殖和迁移能力中起着重要作用。本综述的目的是讨论关于非 Na 依赖性无机磷酸盐转运蛋白的实验结果，并总结它们在 Pi 动态平衡、癌症和其他疾病（如骨关节炎）以及 VC 等过程中的作用。
