Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: Possible reaction of cadmium with the zinc finger domain of Sp1

Kothinti, Rajendra K.; Blodgett, Amy B.; Petering, David H.; Tabatabai, Niloofar M.

doi:10.1016/j.taap.2009.12.038

Cited by 43 publications

(23 citation statements)

References 34 publications

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“…Nephrotoxicity is one of the main adverse effects of cadmium exposure , and references herein). As a consequence, Cd resulted in inhibition of glucose uptake by kidney and glucosuria (Kothinti et al, 2010), and references herein), which may be in the origin of the hypoglycemia we detected in plasma by metabolomics (Table 2). Growing epidemiological studies have suggested a possible link between Cd exposure and diabetes as Cd induced oxidative stress causes suppression of insulin secretion and apoptosis in pancreatic islet -cell .…”

Section: Carbohydrate Metabolismmentioning

confidence: 79%

Functional genomics and metabolomics reveal the toxicological effects of cadmium in Mus musculus mice

et al. 2015

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Abstract:Cadmium (Cd) is an environmental pollutant that accumulates in the organisms causing serious health problems. Over the past decades, "omics" studies have been conducted trying to elucidate changes in the genome, the transcriptome or the proteome after Cd exposure. Metabolomics is relatively new to the "omics" revolution, but has shown enormous potential for investigating biological systems or their perturbations. When metabolomic data are interpreted in combination with genomic, transcriptomic and proteomic results, in the co-called systems biology approach, a holistic knowledge of the organism/process under investigation can be achieved. In this work, transcriptional and proteomic analysis (functional genomics) were combined with metabolomic workflow to evaluate the biological responses caused in Mus musculus mice by Cd (subcutaneous injection for 10 consecutive days). Animals showed high Cd levels in liver and plasma, drastic lipid peroxidation in liver, increased transcription of hepatic genes involved in oxidative stress, metal transport, immune response and lipid metabolism and moderate decreases of DNA repair genes mRNAs. 2DE-DIGE proteomics confirmed changes of hepatic proteins related to stress and immune responses, or involved in energy metabolism, suggesting a metabolic switch in the liver from oxidative phosphorylation to aerobic glycolysis, that was confirmed by metabolomics analysis, via DIMS and GC-MS. This metabolic alteration is particularly important for highly proliferating cells, like tumor cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. The metabolic changes observed in mouse liver by metabolomics and the oxidative stress Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationdetected via functional genomics could be in the base of Cd hepatocarcinogenicity. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation FUNCTIONAL GENOMICS AND METABOLOMICS REVEAL THE TOXICOLOGICAL EFFECTS OF CADMIUM IN Mus musculus MICE

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Section: Carbohydrate Metabolismmentioning

confidence: 79%

Functional genomics and metabolomics reveal the toxicological effects of cadmium in Mus musculus mice

et al. 2015

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“…Thus, human OGG1 (hOGG1), a glycosylase responsible for recognition and excision of the premutagenic 8-oxodG during BER in mammalian cells, was inhibited by cadmium (Potts et al 2003). Even though hOGG1 contains no zinc binding motif itself, its inhibition was shown to be due to diminished DNA binding of the zinc finger containing transcription factor SP1 to the OGG1 promotor (Youn et al 2005), presumably due to displacement of zinc by cadmium (Kothinti et al 2010). Also, a downregulation of DNA repair genes like XPC has been observed recently in cultured cells (Schwerdtle et al 2010) and in vivo (Zhou et al 2004), which may be due to a disturbed transcriptional activity of p53.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Mechanisms in cadmium-induced carcinogenicity: recent insights

2010

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Cadmium is an environmental pollutant,with relevant exposures at workplaces and in the general population. The carcinogenicity has been long established, most evident for tumors in the lung and kidney, but with increasing evidence also for other tumor locations. While direct interactions with DNA appear to be of minor importance, the interference with the cellular response to DNA damage, the deregulation of cell growth as well as resistance to apoptosis have been demonstrated in diverse experimental systems. With respect to DNA repair processes,cadmium has been shown to disturb nucleotide excision repair, base excision repair and mismatch repair; consequences are increased susceptibility towards other DNA damaging agents and endogenous mutagens. Furthermore, cadmium induces cell proliferation, inactivates negative growth stimuli, such as the tumor suppressor protein p53, and provokes resistance towards apoptosis. Particularly the combination of these multiple mechanisms may give rise to a high degree of genomic instability in cadmium-adapted cells, relevant not only for tumor initiation, but also for later steps in tumor development. Future research needs to clarify the relevance of these interactions for low exposure conditions in humans.

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“…Among these low expressed transport-related genes, 10 genes (Slc2a2, Slc5a1, Slc16a2, Slc22a13, Slc22a18, Slc25a11, Slc36a1, Slco6c1, Abca3 and Abcd1) were common between 129/Sv and DBA/2 mice. A previous study showed that Slc5a1 gene expression was downregulated by Cd (Kothinti et al, 2010). To our knowledge, the relationship between Cd and the other remaining genes has not yet been reported.…”

Section: Resultsmentioning

confidence: 78%

Gene expression differences in the duodenum of 129/Sv and DBA/2 mice compared with that of C57BL/6J mice

et al. 2014

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-We compared the cadmium (Cd) concentration in the liver and kidney of different strains of mice after exposure to 50 ppm Cd for 30 days via drinking water. Cd concentration in the liver and kidney of C57BL/6J mice were higher than those of 129/Sv and DBA/2 mice. Since orally ingested heavy metals are absorbed in the small intestine and then widely distributed to target tissues, microarray analyses were performed to compare the expression levels of transport-related genes in the duodenum between C57BL/6J mice and 129/Sv or DBA/2 mice. The expression levels of 9 and 11 genes were elevated more than 2.0-fold and 13 and 12 genes were reduced less than 0.5-fold in 129/Sv mice and DBA/2 mice, respectively. Among these low expressed genes, 10 genes (Slc2a2, Slc5a1, Slc16a2, Slc22a13, Slc22a18, Slc25a11, Slc36a1, Slco6c1, Abca3 and Abcd1) were common between the two types of strains. These results suggest that some of those genes might be involved in Cd absorption and its toxicity.

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Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: Possible reaction of cadmium with the zinc finger domain of Sp1

Cited by 43 publications

References 34 publications

Functional genomics and metabolomics reveal the toxicological effects of cadmium in Mus musculus mice

Functional genomics and metabolomics reveal the toxicological effects of cadmium in Mus musculus mice

Mechanisms in cadmium-induced carcinogenicity: recent insights

Gene expression differences in the duodenum of 129/Sv and DBA/2 mice compared with that of C57BL/6J mice

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