Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: Role of NF‐E2‐related factor‐2

Sakurai, Akihiko; Nishimoto, Michie; Himeno, Seiichiro; Imura, Nobumasa; Tsujimoto, Masafumi; Kunimoto, Manabu; Hara, Shuntaro

doi:10.1002/jcp.20246

Cited by 171 publications

(96 citation statements)

References 47 publications

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“…We propose that, with increased concentrations of H 2 O 2 , GSH is dispensed faster than those synthesized de novo through Nrf2 translocation in SelH shRNA cells when ROS scavenge by SelH is hampered. Increased pNrf2 expression in SelH-deficient cells may further activate the compensatory expression of other antioxidant selenoproteins including thioredoxin reductase-1 and glutathione peroxidase-2 (78,79). On the other hand, SelH may directly induce the de novo synthesis of GSH (27).…”

Section: Discussionmentioning

confidence: 99%

Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation

Cao

Chen

et al. 2014

Journal of Biological Chemistry

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Background: Selenoprotein H (SelH), a proposed redox-responsive DNA-binding protein, is little-studied. Results: SelH shRNA cells display severe proliferation defects and accelerated senescence with abnormal responses to DNA damage and oxidative stress. Conclusion: SelH suppresses senescence and may have important roles in gatekeeping genomic integrity. Significance: Learning how SelH keeps senescence in check is crucial for advancing our understanding linking selenium and aging intervention.

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Section: Discussionmentioning

confidence: 99%

Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation

Cao

Chen

et al. 2014

Journal of Biological Chemistry

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“…11) Briefly, HeLa cells were treated with 10 mM of cadmium chloride or sodium arsenite for 6 h, and then harvested. Twenty micrograms of total RNA isolated from the harvested cells was denatured with formamide, electrophoresed on a 1% agarose gel, and transferred to a PhotoGene nylon membrane (Life Technologies, Inc., Rockville, MD, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

“…10) We have recently reported that cadmium also up-regulates the TrxR1 mRNA level in bovine arterial endothelial cells by activating NF-E2-related factor 2 (Nrf2), a stress-responsive transcriptional factor. 11) Nrf2 is activated by cadmium 12) and is shown to be involved in hemin-induced Trx gene expression 13) as well as TrxR1 gene expression. However, physiological or pathological roles of the induction of TrxR1 gene expression have not been fully elucidated.…”

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confidence: 99%

Short-Interfering RNA-Mediated Silencing of Thioredoxin Reductase 1 Alters the Sensitivity of HeLa Cells toward Cadmium

Nishimoto

Sakaue

Hara

2006

Biological & Pharmaceutical Bulletin

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Cadmium is a ubiquitous environmental contaminant, and it is known to be a highly toxic metal. The level of cadmium in the environment has risen with advances in industrialization, and the role of cadmium in human diseases is of increasing concern. The mechanisms of cadmium toxicity are poorly understood. However, cadmium is thought to cause harmful effects in multiple ways, including production of reactive oxygen species (ROS). 1,2)The thioredoxin (Trx) system, which consists of Trx and Trx reductase (TrxR), is one of the major enzymatic systems modulating intracellular ROS levels. Trx is a small redox-active protein that reduces a wide range of substrates by reversible oxidation of its active center dithiol to a disulfide.3)The Trx system is involved in many cellular functions. 4) Oxidized Trx, which does not exert its biological effects, can be reduced by receiving electrons from NADPH via TrxR. Since TrxR is the only class of enzymes known to reduce oxidized Trx, activity of this enzyme is thought to be an important factor in regulating the activity of the Trx system. 5) Mammalian TrxR is a selenoprotein containing a penultimate Cterminal selenocysteine residue essential for its catalytic activity. To date, three mammalian TrxR isozymes have been identified: cytosolic form (TrxR1), mitochondrial form (TrxR2), and testis-specific form (TrxR3).6,7) Among these three isozymes, TrxR1 is the most well characterized and is known to be inducible in response to various stimuli, including peroxynitrite, 8) phorbol ester, interleukin 1b, 9) and tumor necrosis factor a. 10)We have recently reported that cadmium also up-regulates the TrxR1 mRNA level in bovine arterial endothelial cells by activating NF-E2-related factor 2 (Nrf2), a stress-responsive transcriptional factor. 11) Nrf2 is activated by cadmium 12) and is shown to be involved in hemin-induced Trx gene expression 13) as well as TrxR1 gene expression. However, physiological or pathological roles of the induction of TrxR1 gene expression have not been fully elucidated. In the present study, we attempted to clarify the biological meaning of this induction, that is, to determine whether cadmium-induced TrxR1 plays an important role in cellular defense against cadmium toxicity. It is known to be difficult to overexpress enzymatically active selenoproteins such as TrxR in mammalian cells.14) Therefore, knockdown of TrxR1 by antisense 15) or small interfering RNA (siRNA) 16) seems to be more sound way to examine its intracellular function. Very recently, Seemann and Hainaut reported that transfection of TrxR1 siRNA led to a downregulation of TrxR1 protein with a decrease of over 90% at 48 h after transfection.16) We here silenced the expression of TrxR1 in HeLa cells by using siRNA and examined the effect of gene silencing of TrxR1 on the sensitivity of the cells toward cadmium-induced cell death. MATERIALS AND METHODSCell Culture HeLa (human cervix carcinoma) cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated f...

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“…From their structure, it is apparent that the functions of most selenoproteins should be involved in the redox-related reactions. In fact, the transcription of several selenoproteins such as TrxR1 and GPx2 is regulated by the redox-sensitive transcription factor Nrf2/Keap1 system (14,15). Moreover, severe oxidative stress induces nuclear accumulation of SBP2 and blocks Sec incorporation (2,16 cise functions of many selenoproteins are still unknown.…”

Section: Structure and Activity Of Mammalian Selenoproteinsmentioning

confidence: 99%

Selenoproteins

Holmgren

2009

Journal of Biological Chemistry

596

366

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Selenium is an essential micronutrient for man and animals. The role of selenium has been attributed largely to its presence in selenoproteins as the 21st amino acid, selenocysteine (Sec, U). Sec is encoded by TGA in DNA. A unique mechanism is used to decode the UGA codon in mRNA to co-translationally incorporate Sec into the growing polypeptide because there is no free pool of Sec. In the human genome, 25 genes for selenoproteins have been identified. Selenoproteins such as glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases are involved in redox reactions, and Sec is an active-site residue essential for catalytic activity. Selenoproteins have biological functions in oxidoreductions, redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses.

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Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: Role of NF‐E2‐related factor‐2

Cited by 171 publications

References 47 publications

Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation

Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation

Short-Interfering RNA-Mediated Silencing of Thioredoxin Reductase 1 Alters the Sensitivity of HeLa Cells toward Cadmium

Selenoproteins

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