Inhibition of Na(+)-glucose cotransport in kidney cortical cells by cadmium and copper: protection by zinc.
Properties of the inhibition of Na(+)-glucose cotransport by Cd2+ in mouse kidney cortical cells have been determined. In no case was any inhibition observed before 3 hr. The extent of inhibition was dependent upon both the concentration of Cd2+ and the length of exposure. Kinetic studies showed that metallothionein mRNA induction by Cd2+ was initiated within 1 hr after incubation with Cd2+ began and peaked by 3-6 hr. Metallothionein protein increased more slowly, beginning at 3 hr and continuing for at least 9 hr. The protein had both Cd2+ and Zn2+ bound to it throughout this period. Nevertheless, a pool of nonmetallothionein Cd2+ appeared after 3 hr, coinciding with the onset of inhibition of Na(+)-glucose cotransport, and increased over the next 9 hr. Pretreatment of cells with Zn2+ protected them from the effects of Cd2+ on Na(+)-glucose cotransport. It delayed the onset of inhibition of transport as well as the extent of inhibition. Detailed analysis of the distribution of Cd2+ and Zn2+ in the soluble fraction of these cells showed that the concentration of non-metallothionein bound Cd2+ was not suppressed by the presence of Zn-metallothionein after the onset of exposure to Cd2+. Incubation of cells with larger concentration of Zn2+ and Cu2+ also inhibited Na(+)-glucose cotransport.
Blumenthal
S
S
Department of Nephrology, Veterans Administration Medical Center, Milwaukee, Wisconsin 53295.
Lewand
D
D
Sochanik
A
A
Krezoski
S
S
Petering
D H
DH
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D003300:Copper / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism*; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D012964:Sodium / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D012333:RNA, Messenger; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D012964:Sodium; D005947:Glucose; D015032:Zinc