Gachot B, Poujeol P
Département de Biologie Cellulaire et Moléculaire, CEN Saclay, Gif sur Yvette, France.
Biol Trace Elem Res. 1992 Nov;35(2):93-103. doi: 10.1007/BF02783722.
Zinc, cadmium, and copper are known to interact in many transport processes, but the mechanism of inhibition is widely debated, being either competitive or noncompetitive according to the experimental model employed. We investigated the mechanisms of inhibition of zinc transport by cadmium and copper using renal proximal cells isolated from rabbit kidney. Initial rates of 65Zn uptake were assessed after 0.5 min of incubation. The kinetics parameters of zinc uptake obtained at 20 degrees C were a Jmax of 208.0 +/- 8.4 pmol.min-1.(mg protein)-1, a Km of 15.0 +/- 1.5 microM and an unsaturable constant of 0.259 +/- 0.104 (n = 8). Cadmium at 15 microM competitively inhibited zinc uptake. In the presence of 50 microM cadmium, or copper at both 15 and 50 microM, there was evidence of noncompetitive inhibition. These data suggest that zinc and cadmium enter renal proximal cells via a common, saturable, carrier-mediated process. The mechanisms of the noncompetitive inhibition observed at higher concentrations of cadmium or with copper require further investigation, but may involve a toxic effect on the cytoskeleton.
已知锌、镉和铜在许多转运过程中相互作用，但抑制机制存在广泛争议，根据所采用的实验模型，其抑制机制既可能是竞争性的，也可能是非竞争性的。我们使用从兔肾分离的肾近端细胞，研究了镉和铜对锌转运的抑制机制。孵育0.5分钟后评估65Zn摄取的初始速率。在20℃下获得的锌摄取动力学参数为：Jmax为208.0±8.4 pmol·min-1·(mg蛋白)-1，Km为15.0±1.5 μM，非饱和常数为0.259±0.104（n = 8）。15 μM的镉竞争性抑制锌摄取。在存在50 μM镉或15 μM和50 μM的铜时，有非竞争性抑制的证据。这些数据表明，锌和镉通过共同的、可饱和的、载体介导的过程进入肾近端细胞。在较高浓度的镉或铜存在下观察到的非竞争性抑制机制需要进一步研究，但可能涉及对细胞骨架的毒性作用。
