Differential regulation of mouse kidney sodium-dependent transporters mRNA by cadmium.
Chronic exposure to cadmium can result in renal glycosuria. Previously, we reported that cadmium reduced the relative abundance of the sodium-glucose cotransporter mRNA (Blumenthal et al., Toxicol. Appl. Pharmacol.149, 49-54, 1998). To investigate this phenomenon further, we isolated full-length cDNA clones encoding both high- and low-affinity sodium-dependent glucose transporters SGLT1 and SGLT2, respectively, from cultured mouse kidney cortical cells. We also amplified a fragment of another putative sodium-glucose cotransporter with homology to the known SAAT1/pSGLT2 or SGLT3 from our cultured cells and named it SGLT3. In order to examine the effect of cadmium on these transporters, primary cultures of mouse kidney cortical cells were exposed to micromolar concentrations of cadmium for 24 h and levels of SGLT1, SGLT2, and SGLT3 mRNA were determined by semiquantitative RT-PCR. Five to 10 microM of cadmium inhibited sodium-dependent uptake of the glucose analog, alpha-methyl D-glucopyranoside and progressively reduced the level of SGLT1. Cadmium also inhibited SGLT2 mRNA by 37%, but no further decline was observed at concentrations of cadmium greater than 5 microM. While cadmium inhibited SGLT1 and SGLT2, it significantly stimulated the expression of SGLT3 by fivefold. These results imply that individual sodium-glucose cotransporter mRNA species are not regulated in a similar fashion. In addition, the isolation of three separate SGLT species from these cultures suggests that, in addition to SGLT1 and SGLT2, glucose reabsorption by renal epithelial cells might involve additional glucose transporters such as SGLT3.
Tabatabai
N M
NM
Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, USA.
Blumenthal
S S
SS
Lewand
D L
DL
Petering
D H
DH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008757:Methylglucosides / Q000493:pharmacokinetics; D051379:Mice; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D051247:Sodium-Glucose Transport Proteins; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495675:Slc5a1 protein, mouse; C490299:Slc5a2 protein, mouse; C490297:Slc5a4b protein, mouse; D051247:Sodium-Glucose Transport Proteins; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D002104:Cadmium; C027020:methylglucoside; D012964:Sodium; D005947:Glucose