Adverse effect of cadmium on binding of transcription factor Sp1 to the GC-rich regions of the mouse sodium-glucose cotransporter 1, SGLT1, promoter. Toxicology 2005 Feb 28;207(3):369-82
Date
01/25/2005Pubmed ID
15664265DOI
10.1016/j.tox.2004.10.007Scopus ID
2-s2.0-12344305384 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
Exposure of the kidney to cadmium can cause glucosuria. Effect of cadmium on sodium-glucose cotransporter 1, (SGLT1) mRNA molecules in cultured mouse kidney cortical cells was determined by quantitative competitive RT-PCR. SGLT1 mRNA molecules decreased from 58 x 10(4) microg(-1) total RNA in untreated cells to 29 x 10(4) microg(-1) total RNA in cells exposed to 5 microM cadmium. Increasing cadmium to 7.5 and 10 microM, reduced mRNA molecules to 21 x 10(4) and 12 x 10(4) microg(-1) total RNA, respectively. The half-life of SGLT1 mRNA in control and in cells exposed to 7.5 microM cadmium were almost the same and calculated to be 9.1 h (S.E.+/-2.7) for the former and 8.5 h (S.E.+/-2.2) for the latter. We also analyzed mouse SGLT1 promoter sequences and identified two conserved Sp1 binding sites. The Sp1 binding sequences were used as probes in electrophoretic mobility shift assay (EMSA) with nuclear proteins from cultured cells. Intensity of complexes of the 5' and the 3' Sp1 probes with nuclear Sp1 from cells treated with 7.5 microM cadmium were 84% (S.E.+/-4) and 61% (S.E.+/-14) of controls, respectively. Cadmium had no effect on expression of Sp1 mRNA or protein level. Cadmium-induced inhibition of glucose uptake in kidney may be the result of transcriptional down-regulation of SGLT1 mediated through modification of Sp1 binding to its promoter.
Author List
Tabatabai NM, Blumenthal SS, Petering DHAuthor
Samuel S. Blumenthal MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Binding Sites
Cadmium
Cadmium Poisoning
Cells, Cultured
Dose-Response Relationship, Drug
Down-Regulation
Humans
Kidney Cortex
Membrane Glycoproteins
Mice
Molecular Sequence Data
Monosaccharide Transport Proteins
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Nucleic Acid
Sodium-Glucose Transporter 1
Sp1 Transcription Factor
