Markovich D, Knight D
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Am J Physiol. 1998 Feb;274(2):F283-9. doi: 10.1152/ajprenal.1998.274.2.F283.
Heavy metal intoxication leads to a number of reabsorptive and secretory defects in renal transport systems. We have studied the effects of several heavy metals on the expression of the renal Na-Si cotransporter NaSi-1. NaSi-1 cRNA was injected into Xenopus oocytes, and Na-Si cotransport activity was measured in the presence of mercury, lead, cadmium, or chromium. Mercury strongly inhibited NaSi-1 transport irreversibly by reducing both maximal velocity (Vmax) and Michaelis constant (Km) for inorganic sulfate (Si). Lead inhibited NaSi-1 transport reversibly by decreasing Vmax but not Km for Si. Cadmium showed weak reversible inhibition of NaSi-1 transport by decreasing only NaSi-1 Vmax. Chromium strongly inhibited NaSi-1 cotransport reversibly by reducing Km for Si by sevenfold, most probably by binding to the Si site, due to the strong structural similarity between the CrO4(2-) and SO4(2-) substrates. In conclusion, this study presents an initial report demonstrating heavy metals inhibit renal brush border Na-Si cotransport via the NaSi-1 protein through various mechanisms and that this blockade may be responsible for sulfaturia following heavy metal intoxication.
重金属中毒会导致肾转运系统出现多种重吸收和分泌缺陷。我们研究了几种重金属对肾钠-硅共转运蛋白NaSi-1表达的影响。将NaSi-1 cRNA注射到非洲爪蟾卵母细胞中，并在汞、铅、镉或铬存在的情况下测量钠-硅共转运活性。汞通过降低无机硫酸盐（Si）的最大速度（Vmax）和米氏常数（Km），不可逆地强烈抑制NaSi-1转运。铅通过降低Si的Vmax但不改变Km，可逆地抑制NaSi-1转运。镉仅通过降低NaSi-1的Vmax，对NaSi-1转运表现出微弱的可逆抑制。铬通过将Si的Km降低7倍，可逆地强烈抑制NaSi-1共转运，最有可能是由于CrO4(2-)和SO4(2-)底物之间的强结构相似性，铬与Si位点结合。总之，本研究首次报道了重金属通过各种机制通过NaSi-1蛋白抑制肾刷状缘钠-硅共转运，并且这种阻断可能是重金属中毒后出现硫尿症的原因。
