Cadmium-regulated Genes from the NematodeCaenorhabditis elegans

Liao, Vivian Hsiu‐Chuan; Freedman, Jonathan H.

doi:10.1074/jbc.273.48.31962

Cited by 99 publications

(35 citation statements)

References 66 publications

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“…The reverse transcriptase-PCR protocol of differential display was used to identify new cadmium-responsive genes in C. elegans (17). Here we report on the cloning and analysis of a novel cadmium-inducible gene, designated cdr-1.…”

Section: Discussionmentioning

confidence: 99%

“…Growth of C. elegans-The Bristol N2 strain of C. elegans was grown on NGM agar plates at 20°C as previously described (17). To obtain large quantities of C. elegans, nematodes were grown in liquid S medium using Escherichia coli OP50 as a food source.…”

Section: Methodsmentioning

confidence: 99%

“…Isolation of the CDR-1 cDNA-The four ESTs identified by differential display that are derived from CDR-1 (DDRT2, DDRT7, DDRT16, and DDRT26; accession numbers: AF071362, AF071398, AF0771356, and AF071379, respectively) are between 217 and 240 bp in length and come from the 3Ј-end of the mRNA (17). The full-length sequence of CDR-1 was obtained using the 5Ј-rapid amplification of complementary DNA ends (5Ј-RACE) protocol as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

“…In the collection of cadmium-responsive C. elegans ESTs identified by differential display, four were derived from an identical mRNA (17). Here we describe the isolation and characterization of the full-length mRNA and the gene, designated cdr-1 (cadmium-responsive gene family), from which the ESTs were derived.…”

mentioning

confidence: 99%

“…Forty-eight differentially expressed mRNAs, which correspond to the products of thirty-two independent genes, were identified in the non-parasitic nematode Caenorhabditis elegans (17).…”

mentioning

confidence: 99%

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Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Liao¹,

Dong²,

Freedman³

2002

Journal of Biological Chemistry

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Cadmium is an environmental contaminant that is both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-response proteins. We previously reported the identification of 48 cadmium-inducible mRNAs in the nematode Caenorhabditis elegans. Here we describe a new cadmium-responsive gene, designated cdr-1, whose rate and level of inducible expression parallel those of the C. elegans metallothioneins. The CDR-1 mRNA contains an open reading frame of 831 bp and encodes a predicted 32-kDa, integral membrane protein. Following cadmium exposure, cdr-1 is transcribed exclusively in intestinal cells of post-embryonic C. elegans. In vivo, the CDR-1 protein is targeted specifically to the intestinal cell lysosomes. cdr-1 transcription is significantly induced by cadmium but not by other tested stressors. These results indicate that cdr-1 expression is regulated by cadmium and in a cell-specific fashion. Inhibition of CDR-1 expression renders C. elegans susceptible to cadmium toxicity. In conclusion, cdr-1 defines a new class of cadmium-inducible genes and encodes an integral membrane, lysosomal protein. This protein functions to protect against cadmium toxicity.The transition metal cadmium is considered a serious occupational and environmental health threat. It is continuously introduced into the atmosphere through the smelting of ores and the burning of fossil fuels and is commonly found in "Superfund" clean-up sites (1-3). Humans are exposed to cadmium primarily via inhalation and the ingestion of cadmium-containing foods (4). Toxicological responses of cadmium exposure include kidney damage, respiratory diseases, neurological disorders, and lung, kidney, prostate, and testicular cancers (4).Cadmium induces intracellular damage via the (a) nonspecific inactivation/denaturation of proteins, by binding to free sulfhydryl residues; (b) displacement of zinc co-factors from a variety of proteins, including transcription factors; and (c) generation of reactive oxygen species, which ultimately oxidize DNA, proteins, and lipids. Although cadmium itself is not redox active in vivo and cannot directly catalyze the reduction of molecular oxygen, it has been suggested that the production of reactive oxygen species is a consequence of a cadmium-induced depletion of cellular glutathione or the inactivation of copper/ zinc-superoxide dismutase (5, 6).To attenuate the toxic effects of cadmium, cells respond by increasing the steady-state levels of a variety of proteins. The functions of these proteins can be broadly defined, because those that repair intracellular damage or those that remove the toxicants (e.g. cadmium, reactive oxygen species). To remove toxicants, cells activate the transcription of genes that encode proteins that are involved in scavenging reactive oxygen species, including heme oxygenase, ␥-glutamylcysteine synthetase, superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase (7-11). Cadmium is esse...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Forty-eight differentially expressed mRNAs, which correspond to the products of thirty-two independent genes, were identified in the non-parasitic nematode Caenorhabditis elegans (17).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Liao¹,

Dong²,

Freedman³

2002

Journal of Biological Chemistry

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Cloning genes whose levels of expression are altered by metals: Implications for human health research

Rossman

2000

Am. J. Ind. Med.

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Comparative toxicology of mercurials in Caenorhabditis elegans

McElwee

Freedman

2011

Enviro Toxic and Chemistry

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Mercury is a toxic metal that can exist in multiple chemical species. Humans are commonly exposed to methylmercury and mercury vapor, which is converted to mercuric mercury in the body. Despite years of research, there is a paucity of information on the similarity and differences in the mechanisms of mercury toxicity. The relative toxicity of mercuric chloride (HgCl2) and methylmercury chloride (MeHgCl) in C. elegans was determined using assays that measured growth, feeding, reproduction, and locomotion. The effect of HgCl2 and MeHgCl on the expression of several archetypal stress-response genes was also determined. There was no significant difference between the EC50s of the two mercurials on C. elegans growth. However, MeHgCl was more toxic to C. elegans than HgCl2 when assessing feeding, movement and reproduction, all of which require proper neuromuscular activity. Methylmercury chloride exposure resulted in increased steady-state levels of the stress response genes at lower concentrations than HgCl2. In general, MeHgCl was more toxic to C. elegans than HgCl2, particularly when assaying behaviors that require neuromuscular function.

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Cadmium-regulated Genes from the NematodeCaenorhabditis elegans

Cited by 99 publications

References 66 publications

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Molecular Characterization of a Novel, Cadmium-inducible Gene from the Nematode Caenorhabditis elegans

Cloning genes whose levels of expression are altered by metals: Implications for human health research

Comparative toxicology of mercurials in Caenorhabditis elegans

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