Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways

Mendelev, Natalia; Witherspoon, Sam M.; Li, P. Andy

doi:10.1016/j.expneurol.2009.09.008

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…Altered selenoprotein expression has previously been reported to affect p53 metabolism. Overexpression in mouse neuronal cells of selenoprotein H, a 13 kDa homolog of SEPW1 with a similar Trx-like Sec active site, suppressed the increase in p53 induced by UV radiation and protected cells from apoptosis [Mendelev et al, 2009]. This is similar to our results insofar as selenoprotein H expression and p53 levels were inversely related.…”

Section: Discussionsupporting

confidence: 90%

Selenoprotein W depletion induces a p53‐ and p21‐dependent delay in cell cycle progression in RWPE‐1 prostate epithelial cells

Hawkes

Printsev

Alkan

2011

J of Cellular Biochemistry

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The anticancer activity of selenium (Se) has been demonstrated in myriad animal and in vitro studies, yet the mechanisms remain obscure. The main form of Se in animal tissues is selenocysteine in selenoproteins, but the relative importance of selenoproteins versus smaller Se compounds in cancer protection is unresolved. Selenoprotein W (SEPW1) is a highly conserved protein ubiquitously expressed in animals, bacteria, and archaea. SEPW1 depletion causes a delay in cell cycle progression at the G1/S transition of the cell cycle in breast and prostate epithelial cells. Tumor suppressor protein p53 is a master regulator of cell cycle progression and is the most frequently mutated gene in human cancers. p53 was increased in SEPW1 silenced cells and was inversely correlated with SEPW1 mRNA in cell lines with altered SEPW1 expression. Silencing SEPW1 decreased ubiquitination of p53 and increased p53 half-life. SEPW1 silencing increased p21(Cip1/WAF1/CDKN1A), while p27 (Kip1/CDKN1B) levels were unaffected. G1-phase arrest from SEPW1 knockdown was abolished by silencing p53 or p21. Cell cycle arrest from SEPW1 silencing was not associated with activation of ATM or phosphorylation of Ser-15 in p53, suggesting the DNA damage response pathway was not involved. Silencing GPX1 had no effect on cell cycle, suggesting that G1-phase arrest from SEPW1 silencing was not due to loss of antioxidant protection. More research is required to identify the function of SEPW1 and how it affects stability of p53.

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Section: Discussionsupporting

confidence: 90%

Selenoprotein W depletion induces a p53‐ and p21‐dependent delay in cell cycle progression in RWPE‐1 prostate epithelial cells

Hawkes

Printsev

Alkan

2011

J of Cellular Biochemistry

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“…In a similar manner, SEPH overexpression protects cells from ultraviolet b (UV-B) irradiation by suppressing p53 activation (43,44). At the molecular level, up-regulation of SEPH triggers an AKT-PKA-CREB pathway that culminates in the activation of PGC1α and NRF1, which stimulates mitochondrial biogenesis, leading to enhanced oxygen consumption and respiration (44)(45)(46). Conversely, knockdown of SEPH expression renders cancer cells susceptible to H 2 O 2 (32).…”

Section: Discussionmentioning

confidence: 99%

Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Cox

Tsomides

Kim

et al. 2016

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

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Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels.

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“…Chromatin immunoprecipitation experiments demonstrated SelH binds to sequences containing heat shock and/or stress response elements, suggesting SelH may function in a regulatory role in response to redox status. Overexpression of SelH demonstrates neuroprotection against UVB-induced cell death in neurons in culture and increases the levels of mitochondrial biogenesis regulators, mitochondrial cytochrome c content, mitochondria mass and enhanced respiration [135]. SelH may transduce oxidant signals by modulating gene expression.…”

Section: Function Of Selenoproteinsmentioning

confidence: 99%

Selenium. Role of the Essential Metalloid in Health

Kurokawa

Berry

2013

Metal Ions in Life Sciences

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Selenium is an essential micronutrient in mammals, but is also recognized as toxic in excess. It is a non-metal with properties that are intermediate between the chalcogen elements sulfur and tellurium. Selenium exerts its biological functions through selenoproteins. Selenoproteins contain selenium in the form of the 21st amino acid, selenocysteine (Sec), which is an analog of cysteine with the sulfur-containing side chain replaced by a Se-containing side chain. Sec is encoded by the codon UGA, which is one of three termination codons for mRNA translation in non-selenoprotein genes. Recognition of the UGA codon as a Sec insertion site instead of stop requires a Sec insertion sequence (SECIS) element in selenoprotein mRNAs and a unique selenocysteyl-tRNA, both of which are recognized by specialized protein factors. Unlike the 20 standard amino acids, Sec is biosynthesized from serine on its tRNA. Twenty-five selenoproteins are encoded in the human genome. Most of the selenoprotein genes were discovered by bioinformatics approaches, searching for SECIS elements downstream of in-frame UGA codons. Sec has been described as having stronger nucleophilic and electrophilic properties than cysteine, and Sec is present in the catalytic site of all selenoenzymes. Most selenoproteins, whose functions are known, are involved in redox systems and signaling pathways. However, several selenoproteins are not well characterized in terms of their function. The selenium field has grown dramatically in the last few decades, and research on selenium biology is providing extensive new information regarding its importance for human health.

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Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways

Cited by 26 publications

References 44 publications

Selenoprotein W depletion induces a p53‐ and p21‐dependent delay in cell cycle progression in RWPE‐1 prostate epithelial cells

Selenoprotein W depletion induces a p53‐ and p21‐dependent delay in cell cycle progression in RWPE‐1 prostate epithelial cells

Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Selenium. Role of the Essential Metalloid in Health

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