Selectivity of organ response to cadmium injury and various protective measures

Gunn, Samuel A.; Gould, Thelma Clark; Anderson, Winston A.

doi:10.1002/path.1700960110

Cited by 85 publications

(25 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that Cd-induced testicular necrosis is common across all animal species having testes: rodents, opossum, armadillos, frogs, pigeons, roosters, and fish (12-17). Cellular events that precede Cd-induced testicular toxicity indicate that vascular endothelial cell injury is the earliest and, perhaps, the causative event (16,(18)(19)(20)(21)(22)(23)(24).Some inbred mouse strains are resistant to Cd-induced testicular toxicity (25). The resistance phenotype segregates largely as an autosomal-recessive Mendelian trait, and the gene responsible for the trait was named Cdm (26).…”

mentioning

confidence: 99%

“…It is known that Cd-induced testicular necrosis is common across all animal species having testes: rodents, opossum, armadillos, frogs, pigeons, roosters, and fish (12)(13)(14)(15)(16)(17). Cellular events that precede Cd-induced testicular toxicity indicate that vascular endothelial cell injury is the earliest and, perhaps, the causative event (16,(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis

Dalton

Wang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

267

234

View full text Add to dashboard Cite

Testicular necrosis is a sensitive endpoint for cadmium (Cd 2؉ , Cd) toxicity across all species tested. Resistance to Cd-induced testicular damage is a recessive trait assigned to the Cdm locus on mouse chromosome 3. We first narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region from two sensitive and two resistant inbred strains demonstrated a 400-kb haplotype block consistent with the Cd-induced toxicity phenotype; in this region is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8 encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of intracellular Cd influx and accumulation and 30-fold increase in sensitivity to Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions have no nucleotide differences between two sensitive and two resistant strains of mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the vascular endothelial cells of the testis of the sensitive strains of mice but absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene, defining sensitivity to Cd toxicity specifically in vascular endothelial cells of the testis. metal influx ͉ vascular endothelial cells ͉ solute carrier gene superfamily ͉ in situ hybridization C d is a toxic and carcinogenic nonessential metal (1), which can enter the body through the intestine, skin, and lung and accumulates in the kidney (1-3). The level of Cd in the environment has risen with advances in industrialization, and the role of Cd in human disease is of increasing concern. The mechanisms of Cd toxicity are poorly understood, although it is known that Cd exerts its effects intracellularly, and there are polypeptides such as metallothionein (4) and reduced glutathione (5) that bind Cd and afford protection. The subcellular events by which Cd is taken up by cells or removed from cells remain obscure, although such knowledge could provide potential therapeutic targets for protection or intervention against Cd toxicity. Several proteins transport Cd into bacteria, yeast, plants, and mammalian cells in culture (6-11), but their specific roles in causing toxicity are unclear; these studies underscore the difficulties in extrapolating from observations in cell culture to the intact animal.Nature has provided a fascinating genetic system as a foothold into identifying a gene involved in Cd toxicity. It is known that Cd-induced testicular necrosis is common across all animal species having testes: rodents, opossum, armadillos, frogs, pigeons, roosters, and fish (12-17). Cellular events that precede Cd-induced testicular toxicity indicate that vascular endothelial cell injury is the earliest and, perhaps, the causative event (16,(18)(19)(20)(21)(22)(23)(24).Some inbred mouse strains are resistant to Cd-induced testicular toxicity (25). The resistance phenotype segregates largely as a...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis

Dalton

Wang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

267

234

View full text Add to dashboard Cite

show abstract

“…Its toxicity is known to be counteracted by selenium (Perizek et at., 1971;Sugawara et al, 1989) which has also been shown to reduce the plant availability of cadmium and may also affect other aspects of its toxico-kinetics (Oldfield, 1992;Zakaria et al, 1993). Although the mechanism of the Se-Cd interaction remains unclear, the protective effects of selenium have been referred to the formation of non toxic Se-Cd complexes (Gunn et al, 1968;Chen et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Effect of selenite and selenate on plant uptake of cadmium by kidney bean(Phaseolus mungo)with reference to Cd—Se interaction

Shanker

Mishra

Srivastava

et al. 1995

Chemical Speciation & Bioavailability

View full text Add to dashboard Cite

Pot culture experiments have been conducted to study the effect of selenite and selenate pretreatment on the uptake and translocation of root-absorbed cadmium in the kidney bean plant, irrigated with 2 1-Lg mL -1 of Cd. A statistically significant reduction in cadmium uptake with increasing concentration of selenite and selenate (0.5-6.0 1-Lg mL -1 ) has been observed. Selenite treatment is found to be more effective in decreasing cadmium uptake.

show abstract

“…This suggested that selenium diverted cadmium from its usual target in the testes. Cadmium concentrations in other tissues were also altered, but the most pronounced change was in plasma, which showed a 30-to 50-fold increase in cadmium levels over control (4,5). also altered by selenium (6,7), and a Cd-Secontaining moiety appeared which moved at the void volume of G-75.…”

Section: Introductionmentioning

confidence: 93%

Interaction between cadmium and selenium in rat plasma

Gasiewicz¹,

Smith²

1978

Environ Health Perspect

View full text Add to dashboard Cite

The metabolism of 75Se-labeled SeO32-and its conversion by intact rat erythrocytes in vitro to a form which complexes with Cd and plasma proteins were studied. By utilizing both excess ethylmaleimide to lower erythrocyte reduced glutathione (GSH) concentrations, it was shown that the uptake and metabolism of SeO32-were GSH-dependent, the probable intermediate being glutathione selenotrisulfide (GSSeSG). Secondary release of selenium by rat erythrocytes had no relation to the erythrocyte transport of oxidized glutathione (GSSG). While fluoride depressed and chromate increased GSSG transport, chromate, a glutathione reductase inhibitor, decreased selenium release. This release appeared to be secondary to a reaction catalyzed by glutathione reductase. The similarity of 150 values for chromate's inhibition of glutathione reductase and for the inhibition of selenium release further suggested a relationship between these two events. H2Se or a similar product of GSSeSG reduction is proposed to be the active product of SeO32-metabolism by rat erythrocytes. By use of gel-filtration and ion-exchange methods it was noted that the incubation of H2Se with cadmium and plasma produced a Cd-Se complex indistinguishable from that produced by incubation of Cd, SeO32-, plasma, and erythrocytes in vitro, or that noted following the administration of Cd and SeO3 in vivo. A mechanism whereby the tissue distribution and toxicity of cadmium are altered by selenium is suggested.

show abstract

Selectivity of organ response to cadmium injury and various protective measures

Cited by 85 publications

References 10 publications

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis

Effect of selenite and selenate on plant uptake of cadmium by kidney bean(Phaseolus mungo)with reference to Cd—Se interaction

Interaction between cadmium and selenium in rat plasma

Contact Info

Product

Resources

About