Vol. 285, Issue 3, 1039-1050, June 1998

Role of Extracellular Thiols in Accumulation and Distribution of Inorganic Mercury in Rat Renal Proximal and Distal Tubular Cells¹

Lawrence H. Lash, David A. Putt and Rudolfs K. Zalups

Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L., D.A.P.), and Division of Basic Medical Sciences, Mercer University, School of Medicine, Macon, Georgia (R.K.Z.)

Distribution of inorganic mercury (Hg) into both acid-soluble and protein-bound fractions of proximal tubular (PT) cells from the rat increased with increasing concentrations of Hg up to 10 µM. Little correlation was found between subcellular distribution of Hg and dose in distal tubular (DT) cells. Cellular accumulation of Hg was rapid, reaching equilibrium values by 10 to 15 min. Cellular content of Hg was significantly higher in PT cells than in DT cells at 1 µM Hg. To assess the effect of extracellular thiols on the intracellular accumulation of Hg, PT and DT cells were coincubated with Hg and cysteine, glutathione (GSH), bovine serum albumin (BSA) or 2,3-dimercapto-1-propanesulfonic acid (DMPS) in a 4:1 thiol:Hg molar ratio. Coexposure with Hg and cysteine increased intracellular accumulation of Hg in PT cells at 0.1 µM Hg relative to exposure to Hg alone, consistent with an Hg-cysteine conjugate being a transport form of Hg. In contrast, coexposure with Hg and BSA or DMPS markedly decreased accumulation of Hg relative to cells exposed to Hg alone in both cell types. Coexposure with Hg and GSH also decreased accumulation of Hg relative to exposure to Hg alone, but the decrease was less than coexposure with either BSA or DMPS, suggesting that either an Hg-GSH complex may be a transport form or that some of the Hg-GSH complexes were degraded to Hg-cysteine by the action of brush-border membrane enzymes. These results demonstrate that extracellular thiols markedly alter the renal accumulation of Hg and suggest that some Hg-thiol conjugates may be important physiological transport forms of Hg in the kidney.