Renal Na-Si cotransporter NaSi-1 is inhibited by heavy metals.
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.
Markovich
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Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Knight
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D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D027682:Cation Transport Proteins; D002857:Chromium / Q000494:pharmacology; D005260:Female; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D007854:Lead / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D018075:RNA, Complementary; D012964:Sodium / Q000378:metabolism*; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism*; D027981:Symporters; D014162:Transfection; D014982:Xenopus laevis
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008670:Metals; D018075:RNA, Complementary; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D002104:Cadmium; D002857:Chromium; D007854:Lead; D012964:Sodium; D008628:Mercury