Cadmium decreases SGLT1 messenger RNA in mouse kidney cells

Mouse renal cortical tubule cells in primary culture exposed to cadmium (Cd2+) develop decreased Na(+)-glucose cotransport activity as measured by uptake of the glucose analogue alpha-methyl-glucoside. RNA was isolated from kidney cell cultures, and after reversed transcription, the DNA was amplified with primers to rat SGLT1 (the high affinity isoform of the sodium glucose cotransporter) and mouse beta-actin. Only one product was identified after amplification with the rat SGLT1 primers, which on sequencing was 96% identical to rat SGLT1. Compared to beta-actin, the intensity of the SGLT1 message declined progressively as CdCl2 concentration in the medium increased from 0 to 10 microM. Similar decreases in SGLT1 mRNA were also observed as media zinc (Zn2+) concentrations rose from 0 to 75 microM or as copper (Cu) concentrations increased from 0 to 150 microM. Exposure to 8 microM Cd as Cd-metallothionein (Cd7-MT) also caused a fall in relative SGLT1 mRNA abundance, and at nearly identical internal Cd concentrations of 40-43 pmol/microgram DNA, both Cd7-MT and CdCl2 reduced SGLT1 mRNA to 33% of control. In general, the fall in SGLT1 mRNA was more rapid than the decline in Na(+)-dependent glucose uptake after cells were exposed to Cd2+. These findings suggest that the effects of Cd2+ and other metals on renal glucose transport are related to decreased expression of SGLT1 message.