Effect of Cadmium on the Expression of ABCB1 Transporter in Human Proximal Tubular Cells

Abstract

Cadmium (Cd) is an ecotoxic heavy metal that predominantly causes renal failure. Proximal tubular cell damage is typical of chronic Cd toxicity. Proximal tubular cells play important roles in maintaining a stable balance of body chemicals through the functions of various transporters. ABC transporter subfamily B member 1 [ABCB1; also called MDR1 (multiple drug resistance 1)], one of the ATP binding cassette (ABC) multidrug efflux transporters, is expressed in the proximal tubular epithelium and is involved in the extracellular clearance of various chemicals. In this study, we demonstrate that Cd significantly increases the levels of ABCB1 mRNA and P-glycoprotein protein (the ABCB1 gene product) in the HK-2 human proximal tubular cells. Our results suggest that Cd affects the transportation function in the proximal tubules. However, ABCB1 knockdown did not affect Cd toxicity in the HK-2 cells. Therefore, the Cd-induced increase in ABCB1 may affect the transportation function in the kidney but not the Cd toxicity.