Alteration of DNA binding activity of transcription factors in NRK-52E rat proximal tubular cells treated with cadmium

Tokumoto, Maki; Lee, Jin‐Yong; Fujiwara, Yasuyuki; Satoh, Masahiko

doi:10.2131/jts.39.735

Cited by 14 publications

(20 citation statements)

References 23 publications

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“…Cadmium persists in the human body because it cannot be easily excreted and its concentration increases with age (Ikeda et al, 2004). An epidemiological survey reported that higher intake of cadmium is associated with a higher incidence of renal impairment (Heilmaier et al, 1987;Lee et al, 2013;Miura et al, 2013;Summer et al, 1986;Tokumoto et al, 2014); thus, the health problems caused by cadmium are a global concern.…”

Section: Introductionmentioning

confidence: 99%

FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation

Takahashi

Kuge

et al. 2014

J. Toxicol. Sci.

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-Cadmium-induced cell death is associated with endoplasmic reticulum (ER) stress. We previously found that inhibition of FBXO6 expression, which is a ubiquitin ligase involved in ER-associated protein degradation (ERAD), induces high sensitivity to cadmium in HEK293 cells. However, the precise role of FBXO6 in ER stress remains unexplored. In this study, we investigated the role of FBXO6 in cadmium-induced ER stress in HEK293 cells. Our results showed that the cadmium-induced increase in expression of the ER stress marker proteins, BiP and CHOP, was further enhanced by inhibiting FBXO6 expression. Cadmium-induced c-Jun phosphorylation was also markedly increased by inhibition of FBXO6 expression. However, this c-Jun phosphorylation was almost entirely abolished by inhibition of c-Jun N-terminal kinase 1 (JNK1) expression. The level of high cadmium sensitivity induced by inhibition of FBXO6 expression was markedly lower in the JNK1-ablated cells than in the control cells. In addition, cadmium elevated the cellular level of ERAD substrate proteins, and this elevation was further enhanced by inhibiting FBXO6 expression. These results suggest that FBXO6 might inhibit cadmium-induced ER stress by functioning as a ubiquitin ligase in the ERAD system, thereby attenuating the cell death induced by subsequent JNK1 activation.

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Section: Introductionmentioning

confidence: 99%

FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation

Takahashi

Kuge

et al. 2014

J. Toxicol. Sci.

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“…Because of a lack of Ub conjugation, p53 is accumulated in the cells in the presence of Cd. 26,27) In HK-2 cells, among the UBE2D family, Cd only inhibited the expression of UBE2D2 and UBE2D4. 27) Lee et al showed that knockdown of both UBE2D2 and UBE2D4 resulted in the accumulation of p53 equivalent to Cd-induced p53.…”

Section: Downregulates Ube2d Family Gene Expression Via Suppressiomentioning

confidence: 99%

“…26,27) In HK-2 cells, among the UBE2D family, Cd only inhibited the expression of UBE2D2 and UBE2D4. 27) Lee et al showed that knockdown of both UBE2D2 and UBE2D4 resulted in the accumulation of p53 equivalent to Cd-induced p53. 27) Cd increased the level of phosphorylated p53 in the nuclei of HK-2 cells, and knockdown of p53 prevented Cd-induced apoptosis.…”

Section: Downregulates Ube2d Family Gene Expression Via Suppressiomentioning

confidence: 99%

Transcription Factors and Downstream Genes in Cadmium Toxicity

Tokumoto

Lee

Satoh

2019

Biological & Pharmaceutical Bulletin

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Cadmium (Cd) is a harmful heavy metal widely present in the environment which can cause severe kidney damage. The proximal tubular cells are the main target of renal Cd toxicity. The consequences of Cd cytotoxicity involve apoptosis and necrosis. Recently, we and others have focused on how Cd affects transcription factors and the regulation of their target genes. Those studies showed that transcription factors initiate numerous pathways upon Cd exposure, leading to apoptosis, autophagic cell death, disruption of cell-cell adhesion, and generation of mitochondrial reactive oxygen species. Of particular note, Cd induces endoplasmic reticulum stress, resulting in not only apoptosis but also autophagic dysregulation, which can trigger cell damage. In some cases, however, Cd-regulated transcription factors can induce cell survival signaling. This review centers on our own research to elucidate the transcription factor-downstream gene cascades that are central to Cd-induced renal toxicity.

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“…Furthermore, Cd changes the activities of transcription factors involved in the transcription of UPS-related genes (Tokumoto et al, 2014). UPS plays an important role in maintaining the quality and homeostasis of proteins.…”

Section: Introductionmentioning

confidence: 99%

Effect of gestational cadmium exposure on fetal growth, polyubiquitinated protein and monoubiqutin levels in the fetal liver of mice

et al. 2018

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-Cadmium (Cd) is an environmental pollutant present in contaminated water, food and soil. Cd adversely affects fetal development. We exposed pregnant mice to daily oral doses of 5 and 10 mg/kg Cd and examined fetal growth. It was demonstrated that the exposure to Cd (10 mg/kg) during gestation caused fetal growth retardation (FGR). Investigation of the ubiquitin-proteasome system in fetal livers of mice exposed to gestational Cd revealed increased polyubiquitinated protein accumulation, contrasting with decreased levels of monoubiquitin protein. Moreover, the expression level of Ubc (encoding polyubiquitin C protein) was significantly decreased in 5 and 10 mg/kg Cd-treated groups in comparison with the control group. Therefore, we propose that decrease of monoubiquitin level and accumulation of polyubiquitinated protein in the fetal liver may be important factors in Cd-induced FGR.

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Alteration of DNA binding activity of transcription factors in NRK-52E rat proximal tubular cells treated with cadmium

Cited by 14 publications

References 23 publications

FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation

FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation

Transcription Factors and Downstream Genes in Cadmium Toxicity

Effect of gestational cadmium exposure on fetal growth, polyubiquitinated protein and monoubiqutin levels in the fetal liver of mice

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