The role of Ca2+ in cadmium-induced renal tubular cell injury.
Changes in rat renal proximal tubule cell gene expression were studied in vitro using a cadmium metallothionein (CdMT) exposure model. Increased expression of MT together with alterations in the expression of several other stress protein products were demonstrated by 35S-two-dimensional gel electrophoresis. Stress proteins with estimated molecular masses of 32, 70 and 90 kDa were observed to be increased after 4 h of exposure. These changes preceded the onset of cell injury. Internal stores of Ca2+ were not found to be measurably altered, as measured by the changes in fluorescence of the dye FURA-2. These data suggest that the observed alterations in gene expression are directly mediated by Cd2+ and not secondary to increased availability of Ca2+ within the target cell population, perhaps mediated by the transacting factor which regulates MT synthesis. The calcuria resulting from in vivo exposure to Cd2+ in workers or CdMT exposure in animal models may be secondary to alterations in renal proximal tubule cell gene expression.
Fowler
B A
BA
University of Maryland, Program in Toxicology, Baltimore 21201.
Akkerman
M
M
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000235:genetics; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000502:physiology*; D008954:Models, Biological; D051381:Rats
D002104:Cadmium; D002118:Calcium