Antioxidant and whitening activities of five unripe pear cultivars

The present study was the first evaluation of the arbutin content, antioxidant activity, and whitening function of the unripe pears of five major Korean pear cultivars. Unripe pears were investigated 30 days after florescence for possible utilization as a whitening ingredient, instead of being thrown away for thinning out. Among the five cultivars tested, Gamcheonbae and Manpungbae had significantly higher total phenolics and arbutin contents, while Niitaka had lower values of both total phenolics and arbutin. For whitening activity related to tyrosinase and cellular melanin formation, Manpungbae also showed the strongest tyrosinase inhibition (4.9 %), and achieved 74% reduction of the cellular melanin compared to non-treated cells. These results indicate that unripe pears, especially the Manpungbae cultivar, could be useful for application as a possible natural whitening additive with high arbutin content and excellent whitening activity

Physiochemical, nutritional and functional characterization of 10 different pear cultivars (<i>Pyrus</i> spp.)

This study was performed to compare the physiochemical properties and nutritional components including sugars, amino acids, and minerals of 10 common pear cultivars cultivated in Korea (four Pyrus spp.). Furthermore, the pear cultivars were characterized for functional properties with respect to phenolic compounds by HPLC/DAD analysis and antioxidant activities using DPPH and ABTS assays. Among the 10 pear cultivars that were tested, Niitaka and Hanareum pears show the best physiochemical properties such as higher sugar/acid ratio and proper firmness. They also showed relatively enriched soluble sugar (12.6 ~ 13.0 g/100g FW), amino acid (4.5 ~ 7.3 g/100 g DW) or mineral contents with high K/Na ratio. For functional properties, Niitaka and Hanareum pears have significantly higher contents of total phenolics (240 mg/100 g DW), arbutin (103 ~ 124 mg/100 g DW), and chlorogenic acid (11 mg/100 g DW) as well as strong antioxidant activities (49 % or 86 %) among cultivars. These results indicate that Niitaka, and Hanareum cultivars, could be best for consumption or favorable processing due to excellent product quality and high concentrations of nutritional and functional compounds

Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein

The farnesoid X receptor negatively regulates osteoclastogenesis in bone remodeling and pathological bone loss

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Since the role of FXR in osteoclast differentiation remains ill-defined, we investigated the biological function of FXR on osteoclastogenesis, using FXR-deficient mice. We demonstrated that FXR deficiency increases osteoclast formation in vitro and in vivo. First, FXR deficiency was found to accelerate osteoclast formation via down-regulation of c-Jun N-terminal kinase (JNK) 1/2 expression. Increased expression of peroxisome proliferator-activated receptor (PPAR)γ and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC- 1)β seems to mediate the pro-osteoclastogenic effect of FXR deficiency via the JNK pathway. In addition, we found that FXR deficiency downregulated the expression of interferon-β (IFN-β), a strong inhibitor of osteoclastogenesis, via receptor activator of nuclear factor-kappaB ligand (RANKL). We further suggested that interference of IFN-β expression by FXR deficiency impaired the downstream JAK3-STAT1 signaling pathways, which in turn increased osteoclast formation. Finally, FXR deficiency accelerated unloading- or ovariectomy-induced bone loss in vivo. Thus, our findings demonstrate that FXR is a negative modulator in osteoclast differentiation and identify FXR as a potential therapeutic target for postmenopausal osteoporosis and unloadinginduced bone loss

Methionine restriction extends lifespan of \u3ci\u3eDrosophila melanogaster\u3c/i\u3e under conditions of low amino-acid status

Reduced methionine (Met) intake can extend lifespan of rodents; however, whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino-acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino-acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signalling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino-acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension

The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease

Background/Aims:A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea. Methods:A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption. Results:The subjects were aged 51.7±10.3 years (mean±SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75–0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60–0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend 20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001). Conclusions:The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD

Evolution of selenophosphate synthetases: emergence and relocation of function through independent duplications and recurrent subfunctionalization

Selenoproteins are proteins that incorporate selenocysteine (Sec), a nonstandard amino acid encoded by UGA, normally a stop codon. Sec synthesis requires the enzyme Selenophosphate synthetase (SPS or SelD), conserved in all prokaryotic and eukaryotic genomes encoding selenoproteins. Here, we study the evolutionary history of SPS genes, providing a map of selenoprotein function spanning the whole tree of life. SPS is itself a selenoprotein in many species, although functionally equivalent homologs that replace the Sec site with cysteine (Cys) are common. Many metazoans, however, possess SPS genes with substitutions other than Sec or Cys (collectively referred to as SPS1). Using complementation assays in fly mutants, we show that these genes share a common function, which appears to be distinct from the synthesis of selenophosphate carried out by the Sec- and Cys- SPS genes (termed SPS2), and unrelated to Sec synthesis. We show here that SPS1 genes originated through a number of independent gene duplications from an ancestral metazoan selenoprotein SPS2 gene that most likely already carried the SPS1 function. Thus, in SPS genes, parallel duplications and subsequent convergent subfunctionalization have resulted in the segregation to different loci of functions initially carried by a single gene. This evolutionary history constitutes a remarkable example of emergence and evolution of gene function, which we have been able to trace thanks to the singular features of SPS genes, wherein the amino acid at a single site determines unequivocally protein function and is intertwined to the evolutionary fate of the entire selenoproteome

Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status

Reduced methionine (Met) intake can extend lifespan of rodents, but whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signaling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension

Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDPglucose: glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vitro splenic B cell differentiation. However, Selenof knockout animals show neither enhanced bacterial killing capacity nor antigen-induced systemic IgM activity, suggesting that excess immunoglobulins are not functional. In addition, ER-to-Golgi transport of a target glycoprotein was delayed in Selenof knockout embryonic fibroblasts, and proteomic analyses revealed that Selenof deficiency is primarily associated with antigen presentation and ER-to-Golgi transport. Together, the data suggest that Selenof functions as a gatekeeper of immunoglobulins and, likely, other client proteins that exit the ER, thereby supporting redox quality control of these proteins