SUBCELLULAR TARGETS OF CADMIUM NEPHROTOXICITY - CADMIUM-BINDING TO RENAL MEMBRANE-PROTEINS IN ANIMALS WITH OR WITHOUT PROTECTIVE METALLOTHIONEIN SYNTHESIS

Nephrotoxic effects of cadmium exposure are well established in humans and experimental animals. An early manifestation of such toxicity is calciuria a few hours after injection of CdMT in rats. Protection agai nst calciuria and other adverse effects such as proteinuria (occurring later) is offered by pretreatment with Cd, which effectively induces metallothionein synthesis. In the present experiment, one group of ani mals was given pretreatment with CdCl2 to induce metallothionein synth esis. The comparison group was left without pretreatment. The distribu tion of Cd from a normally nephrotoxic dose of (109)CdMT was studied b y gel chromatography in subcellular fractions of kidney cortex in both groups. In the pretreated animals, Cd-109 in the plasma membrane and microsome fractions of renal cortical cells was mainly bound to metall othionein and other low molecular weight proteins at 4 hr. In nonpretr eated animals the major part of Cd-109 was bound to high molecular wei ght proteins. These findings indicate that membrane proteins may be im portant targets for Cd when inducing nephrotoxicity and that sequester ing of Cd by metallothionein (and other low molecular weight proteins) may be a mechanism of protection.