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Inhibition of Na(+)-glucose cotransport in kidney cortical cells by cadmium and copper: protection by zinc. Toxicol Appl Pharmacol 1994 Dec;129(2):177-87

Date

12/01/1994

Pubmed ID

7992308

DOI

10.1006/taap.1994.1242

Scopus ID

2-s2.0-0028000204 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

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.

Author List

Blumenthal S, Lewand D, Sochanik A, Krezoski S, Petering DH

Author

Samuel S. Blumenthal MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Biological Transport, Active
Cadmium
Cells, Cultured
Copper
Glucose
Kidney Cortex
Kidney Tubules, Proximal
Kinetics
Male
Metallothionein
Mice
Mice, Inbred C57BL
RNA, Messenger
Sodium
Zinc