The intake of flavonols, flavones and isoflavones by Japanese women was calculated from our food-phytochemical composition table. The relationship between intake of these phytochemicals and various anthropometric and blood chemistry data was analyzed in a cross-sectional study. The subjects were 115 women volunteers, aged 29-78 y, living in the northern part of Japan. Each subject completed a 3-d dietary record and received a health check up, including urine and blood sampling for biochemical analysis. Total mean intakes of flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2 mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d). The total intake of flavonoids was inversely correlated with the plasma total cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body mass index and total energy intake. As a single component, quercetin was inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263, P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component among nonnutrient phytochemicals with antioxidant potential in the diet. These results suggest that a high consumption of both flavonoids and isoflavones by Japanese women may contribute to their low incidence of coronary heart disease compared with women in other countries.

Hepatitis C virus (HCV) is a major cause of chronic liver disease that frequently leads to steatosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). HCV core protein is not only a component of viral particles but also a multifunctional protein because liver steatosis and HCC are developed in HCV core gene-transgenic (CoreTg) mice. Proteasome activator PA28␥/REG␥ regulates host and viral proteins such as nuclear hormone receptors and HCV core protein. Here we show that a knockout of the PA28␥ gene induces the accumulation of HCV core protein in the nucleus of hepatocytes of CoreTg mice and disrupts development of both hepatic steatosis and HCC. Furthermore, the genes related to fatty acid biosynthesis and srebp-1c promoter activity were up-regulated by HCV core protein in the cell line and the mouse liver in a PA28␥-dependent manner. Heterodimer composed of liver X receptor ␣ (LXR␣) and retinoid X receptor ␣ (RXR␣) is known to up-regulate srebp-1c promoter activity. Our data also show that HCV core protein enhances the binding of LXR␣/RXR␣ to LXR-response element in the presence but not the absence of PA28␥. These findings suggest that PA28␥ plays a crucial role in the development of liver pathology induced by HCV infection.fatty acid ͉ proteasome ͉ sterol regulatory element-binding protein (SREBP) ͉ RXR␣ ͉ LXR␣ H epatitis C virus (HCV) belongs to the Flaviviridae family, and it possesses a positive, single-stranded RNA genome that encodes a single polyprotein composed of Ϸ3,000 aa. The HCV polyprotein is processed by host and viral proteases, resulting in 10 viral proteins. Viral structural proteins, including the capsid (core) protein and two envelope proteins, are located in the N-terminal one-third of the polyprotein, followed by nonstructural proteins.HCV infects Ͼ170 million individuals worldwide, and then it causes liver disease, including hepatic steatosis, cirrhosis, and eventually hepatocellular carcinoma (HCC) (1). The prevalence of fatty infiltration in the livers of chronic hepatitis C patients has been reported to average Ϸ50% (2, 3), which is higher than the percentage in patients infected with hepatitis B virus and other liver diseases. However, the precise functions of HCV proteins in the development of fatty liver remain unknown because of the lack of a system sufficient to investigate the pathogenesis of HCV. HCV core protein expression has been shown to induce lipid droplets in cell lines and hepatic steatosis and HCC in transgenic mice (4-6). These reports suggest that HCV core protein plays an important role in the development of various types of liver failure, including steatosis and HCC.Recent reports suggest that lipid biosynthesis affects HCV replication (7-9). Involvement of a geranylgeranylated host protein, FBL2, in HCV replication through the interaction with NS5A suggests that the cholesterol biosynthesis pathway is also important for HCV replication (9). Increases in saturated and monounsaturated fatty acids enhance HCV RNA replication, whereas increases in polyunsaturat...

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The protective effect of aG‐Rutin against ferric nitrilotriacetate (Fe‐NTA)‐induced renal damage was studied in male ICR mice. Fe‐NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of αG‐Rutin (50 μmol as rut in/leg) by gastric intubation 30 min after i.p. injection of Fe‐NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe‐NTA (2 mg FeAg/day for the first 3 days and 3 mg Fe/ kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given αG‐Rutin 30 min after each Fe‐NTA treatment. To elucidate the mechanism of protection by αG‐Rutin, the pharmacokinetics and hydroxyl radical‐scavenging effect of αG‐Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5‐dimethyl‐l‐pyrroline‐N‐oxide (DMPO), respectively. When mice were given αG‐Rutin (50 μmol as rutin Ag) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of äG‐Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min. äG‐Rutin inhibited the formation of DMPO‐OH in a concentration‐dependent manner. Further, chelating activity of äG‐Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed äG‐Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe‐NTA.

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ABSTRACT. The keratinocyte, the major component of the epidermis, expresses several proteins that characterize the keratinization during the differentiation. Proliferation and differentiation of cultured human keratinocytes are known to be regulated by the Ca 2+ concentration in the culture medium. However, informations about the rat keratinocyte are relatively limited and their physiology is still an open question. To elucidate the characteristics of the rat keratinocyte, we established rat keratinocyte culture system and examined effects of extracellular calcium concentration on the expression of differentiation-related proteins. Keratinocytes were isolated from the newborn rat skin with 0.25% trypsin, followed by separation with a Percoll density gradient. The separated cells were grown in MCDB153 medium containing several growth factors and Ca 2+ -free fetal bovine serum, then stimulated with Ca 2+ . Immunoblotting demonstrated strong expression of β1 integrin in unstimulated cells, suggesting that the primary culture of rat keratinocytes was successfully established. Expression of desmoglein and transglutaminase was increased by Ca 2+ stimulation, whereas β1 integrin expression was decreased in response to increasing concentrations of Ca 2+ . These observations indicate that cultured rat keratinocytes maintain the ability to differentiate in vitro, which is similar to that of the basal keratinocytes in the epidermis. KEY WORDS: cell culture, desmoglein, differentiation, integrin, keratinocyte.J. Vet. Med. Sci. 64(2): 123-127, 2002 The epidermis consists of multiple layers of keratinocytes. When keratinocytes of the basal layer withdraw from the cell cycle and become committed to the terminal differentiation, they detach from the basement membrane and migrate into the suprabasal layers [1,6,7,12]. During the differentiation, human keratinocytes express several proteins, transglutaminase and substrates of this enzyme such as involucrin and filaggrin, which form the cornified envelope in the keratinized layer of the epidermis. The structure of cell-cell adhesion also changes during the differentiation. Desmosome, a calcium-dependent intercellular adhesion structure, is known to be composed of transmembrane glycoproteins, e.g. desmoglein and desmocollin. These proteins bind to the cytoplasmic plaque proteins plakoglobin, desmoplakin, and are linked to keratin intermediate filaments [2,4,13]. The IgG autoantibodies against desmoglein-1 and -3 cause the epidermal blistering diseases such as pemphigus foliaceous and pemphigus vulgaris [5,[19][20][21] . Recent evidence in human keratinocytes showed these antigenitic epitopes of desmogleins are conformation-dependent [3] and calcium-dependent [22].Integrins are heterodimeric transmembrane receptor that consist of an α and a β subunit, and mediate the attachment of cells to the extracellular matrix or to other cells. Until now, sixteen α and eight β subunits and more than 20 different receptors have been identified. The ligand-binding specificity of an integrin is...

Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolic of almitrine, were examined by light microscopy and transmission electron microscopy. Vacuolar degeneration associated with lamellar inclusions was observed in musculus soleus and m. interossei of the hindlimbs in DFBP-treated rats. The inclusions were also produced within sensory neurons, satellite and Schwann cells, and vascular endothelial cells of thoracic and lumbar dorsal root ganglia as well as muscle spindles of affected muscles. Membrane-bound vacuoles containing electron-dense granules were seen in the peripheral nerves. This study demonstrated neuronal and muscular toxicity of DFBP in rats.