Long G J, Rosen J F
Department of Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Life Sci. 1994;54(19):1395-402. doi: 10.1016/0024-3205(94)00594-x.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to modulate Ca2+ metabolism in several cell types. 1,25(OH)2D3 causes an increase in Ca2+ influx and probably exerts many of its effects via the Ca2+ messenger system. Lead (Pb2+) interacts with and perturbs normal Ca2+ signalling pathways; hence, the purpose of this work was to determine if Pb2+ perturbs 1,25(OH)2D3 modulation of Ca2+ metabolism in ROS 17/2.8 cells, which express receptors for and respond to 1,25(OH)2D3, and to determine the effect of 1,25(OH)2D3 on Pb2+ metabolism in these cells. In both cases three kinetic compartments described the intracellular metabolism of the isotope. These data show that 1 microM Pb2+ inhibits 1,25(OH)2D3 modulated increases in Ca2+ flux, whereas 5 microM Pb2+ increases membrane fluxes, all intracellular Ca2+ pools, and total cell Ca2+. In the Pb2+ metabolism studies it was found that 10 nM 1,25(OH)2D3 increases intracellular Pb2+. Pb2+ appears to disrupt the modulation of intracellular steady-state Ca2+ homeostasis by 1,25(OH)2D3 in a complex, biphasic manner and may therefore perturb functions that are modulated by 1,25(OH)2D3 via the Ca2+ messenger system.
已知1,25 - 二羟基维生素D3（1,25(OH)2D3）可调节多种细胞类型中的Ca2+代谢。1,25(OH)2D3会使Ca2+内流增加，并且可能通过Ca2+信使系统发挥其许多作用。铅（Pb2+）会与正常的Ca2+信号通路相互作用并对其造成干扰；因此，本研究的目的是确定Pb2+是否会干扰ROS 17/2.8细胞中1,25(OH)2D3对Ca2+代谢的调节，该细胞表达1,25(OH)2D3的受体并对其产生反应，同时确定1,25(OH)2D3对这些细胞中Pb2+代谢的影响。在这两种情况下，三个动力学区室描述了同位素的细胞内代谢。这些数据表明，1 microM的Pb2+会抑制1,25(OH)2D3调节的Ca2+通量增加，而5 microM的Pb2+会增加膜通量、所有细胞内Ca2+池以及细胞总Ca2+含量。在Pb2+代谢研究中发现，10 nM的1,25(OH)2D3会增加细胞内Pb2+含量。Pb2+似乎以一种复杂的双相方式破坏了1,25(OH)2D3对细胞内稳态Ca2+平衡的调节，因此可能会干扰由1,25(OH)2D3通过Ca2+信使系统调节的功能。
