Novel mouse models were developed in which the hepatic selenoprotein population was targeted for removal by disrupting the selenocysteine (Sec) tRNA([Ser]Sec) gene (trsp), and selenoprotein expression was then restored by introducing wild type or mutant trsp transgenes. The selenoprotein population was partially replaced in liver with mutant transgenes encoding mutations at either position 34 (...

Malignant melanoma is the most dangerous type of skin cancer. Although recent progress in treatment has been achieved, lack of response, drug resistance and relapse remain major problems. The tumor suppressor p53 is rarely mutated in melanoma, yet it is inactive in the majority of cases due to dysregulation of upstream pathways. Thus, we screened for compounds that can activate p53 in melanoma ...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-1/2 (TRAIL-R1/R2), also known as death receptors, are expressed in a wide variety of tumor cells. Although TRAIL can induce cell apoptosis by engaging its cognate TRAIL-R1/R2, some tumor cells are or become resistant to TRAIL treatment. Monoclonal antibodies (mAbs) against TRAIL-R1/R2 have been developed to use as potentia...

MDA-7/IL-24 was involved in the specific cancer apoptosis through suppression of Bcl-2 expression, which is a key apoptosis regulatory protein of the mitochondrial death pathway. However, the underlying mechanisms of this regulation are unclear. We report here that tumor-selective replicating adenovirus ZD55-IL-24 leads to Bcl-2 S-denitrosylation and concomitant ubiquitination, which take part ...

The intracellular generation of reactive oxygen species, together with the thioredoxin and glutathione systems, is thought to participate in redox signaling in mammalian cells. The activity of thioredoxin is dependent on the redox status of thioredoxin reductase (TR), the activity of which in turn is dependent on a selenocysteine residue. Two mammalian TR isozymes (TR2 and TR3), in addition to ...

Ochratoxin A (OTA), a mycotoxin, is a potent nephrotoxin in humans and animals. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced nephrotoxicity. In this study, the protective effects of selenomethionine against OTA-induced nephrotoxicity were investigated using the porc...

Cysteine (Cys) is inserted into proteins in response to UGC and UGU codons. Herein, we show that supplementation of mammalian cells with thiophosphate led to targeted insertion of Cys at the UGA codon of thioredoxin reductase 1 (TR1). This Cys was synthesized by selenocysteine (Sec) synthase on tRNA([Ser]Sec) and its insertion was dependent on the Sec insertion sequence element in the 3'UTR of ...

Selenoproteins are essential molecules for the mammalian antioxidant network. We previously demonstrated that targeted loss of all selenoproteins in mouse epidermis disrupted skin and hair development, and caused premature death. In the current study, we targeted specific selenoproteins for epidermal deletion to determine whether similar phenotypes developed. Keratinocyte-specific knockout mice...

TRXR) chromosomal position 12q23.3-q24.1 (§, ‡) is a homodimeric selenocysteine-containing enzyme. Secys a selenocysteine residue is an essential TR isozyme component, located near the C-terminus region [cysteine (Cys)-497,Secys-498] of the intracellular, redox cellular environments center in the catalytically active enzyme site, Gly-499 is the actual C-terminal amino acid. In their N-terminal ...

BACKGROUND The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B1 (AFB1)-induced adverse effects in broilers remains unclear. OBJECTIVE This study was designed first to determine whether selenium could reduce AFB1-induced hepatotoxic effects and then to determine whether these effects were due to changes in the CYP450 iso...