Biofactors - Volume 33, issue 1

Authors: Chen, Zhi-Hua | Saito, Yoshiro | Yoshida, Yasukazu | Noguchi, Noriko | Niki, Etsuo

Article Type: Research Article

Abstract: Extracellular signal-regulated protein kinase (ERK), one of the mitogen-activated protein kinase, has been known to be involved in diverse cellular functions. In this work, we found that basically inhibition of this kinase in cultured cells markedly increased the γ-glutamate-cysteine ligase (GCL; EC 6.3.2.2) activity, but without any considerable induction of the GCL genes. The increased GCL activity consequently elevated the cellular GSH level and eventually enhanced the cellular antioxidant capacity. Genetic …inhibition of B-Raf, the upstream of ERK, also resulted in increased GCL activity and GSH level. Recent evidence also suggests that chronic pro-oxidant exposure results in the loss of ERK phosphorylation in vivo. Therefore, the findings in the present study suggest that inhibition of B-Raf/MEK/ERK pathway might be a promising physiological approach to up-regulate GCL activity and GSH. This study would also help us to understand the comprehensive role of the Raf/MEK/ERK pathway in overall physio/pathological conditions. Show more

Keywords: B-Raf/MEK/ ERK, GCL, GSH, phosphorylation/dephosphorylation, oxidative stress

Citation: BioFactors, vol. 33, no. 1, pp. 1-11, 2008

Authors: Parmar, Hamendra Singh | Kar, Anand

Article Type: Research Article

Abstract: Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats. In one study, out of 4 different doses (50–300 mg/kg), 200 mg/kg of MI and 100 mg/kg for other two peel extracts could inhibit lipidperoxidation (LPO) maximally in liver. In the second experiment rats were maintained on …pre-standardized atherogenic diet CCT (supplemented with 4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil) to induce dyslipidemia, hypothyroidism and diabetes mellitus and the effects of the test peel extracts (200 mg/kg of MI and 100 mg/kg for CM and CV for 10 consecutive days) were studied by examining the changes in tissue LPO (in heart, liver and kidney), concentrations of serum lipids, thyroid hormones, insulin and glucose. Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus. A phytochemical analysis indicated the presence of a high amount of polyphenols and ascorbic acid in the test peel extracts suggesting that the beneficial effects could be the result of the rich content of polyphenols and ascorbic acid in the studied peels. Show more

Keywords: Serum lipids, thyroid hormones, insulin, glucose, Mangifera indica, Cucumis melo, Citrullus vulgaris

Citation: BioFactors, vol. 33, no. 1, pp. 13-24, 2008

Authors: Takahashi, Nobuyuki | Kang, Min-Sook | Kuroyanagi, Kayo | Goto, Tsuyoshi | Hirai, Shizuka | Ohyama, Kana | Lee, Joo-Young | Yu, Rina | Yano, Masamichi | Sasaki, Takao | Murakami, Shigeru | Kawada, Teruo

Article Type: Research Article

Abstract: Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-α (PPARα) activation. To examine effects of auraptene on the PPARα activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPARα expression level is very low. In the PPAR ligand …assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPARα chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPARα-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPARα because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPARα-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPARα agonist in hepatocytes and that auraptene may improve lipid abnormality through PPARα activation in the liver. Show more

Keywords: Auraptene, hepatocytes, PPARα, metabolic syndrome

Citation: BioFactors, vol. 33, no. 1, pp. 25-32, 2008

Authors: Potenza, Lucia | Calcabrini, Cinzia | De Bellis, Roberta | Mancini, Umberto | Cucchiarini, Luigi | Dachà, Marina

Article Type: Research Article

Abstract: Quercetin is a well-investigated antioxidant known to protect cells against oxidative nuclear DNA damage. There is no knowledge regarding its effect on oxidative mitochondrial DNA damage. In this study we investigated the effect of quercetin on oxidatively-injured DNA. Cell-free and cell studies were performed. Cell-free analyses carried out on plasmidic DNA showed that quercetin protects from all oxidative challenges used. Cellular studies were carried out on NCTC 2544 cells which were insulted with hydrogen peroxide and …UVC radiations. Nuclear and mitochondrial DNAs were analysed by measuring DNA damage with a quantitative polymerase chain reaction. Quercetin supplementation showed significant genoprotective activity on mitochondrial DNA when hydroperoxide was used. The evidence of the protection afforded by quercetin suggests that this flavonoid may play an important role on mitochondrial genome stability. Show more

Keywords: Quercetin, oxidative damage, mitochondrial DNA, nuclear DNA, NCTC 2544

Citation: BioFactors, vol. 33, no. 1, pp. 33-48, 2008

Authors: Kim, Na-Hyung | Moon, Phil-Dong | Kim, Su-Jin | Choi, In-Young | An, Hyo-Jin | Myung, Noh-Yil | Jeong, Hyun-Ja | Um, Jae-Young | Hong, Seung-Heon | Kim, Hyung-Min

Article Type: Research Article

Abstract: Lactic acid bacteria are known to exert various physiologic functions in humans. In the current study, we investigated the effects of Soypro™, a new soymilk fermented with lactic acid bacteria, like Leuconostoc kimchii, Leuconostoc citreum, and Lactobacillus plantarum, isolated from Kimchi, on adipocyte differentiation in preadipocyte 3T3-L1 cell lines and weight gain or the plasma lipid profile in Sprague-Dawley rats. Adipocyte 3T3-L1 cells treated with Soypro™ (10 μg/ml) significantly reduced …the contents of cellular triglyceride and inhibited cell differentiation by Oil red O staining. Treatment with Soypro™ (10 μg/ml) for an additional two days in adipocytes inhibited the expression of peroxisome proliferator-activated receptor-γ_{2} and CCAAT/enhancer binding protein-α, transcription factors of adipocyte differentiation. Based on these in vitro studies, we examined the anti-obesity effect of Soypro™ in rats for six weeks. Soypro™ had no significant effect on high-fat diet-induced increases in body weight, food intake, or feed gain ratio. However, the administration of Soypro™ significantly reduced the concentration of the plasma low density lipoprotein cholesterol. Changes in the plasma levels of total cholesterol and glucose were inclined to decrease in Soypro™ administrated groups compared with saline treated group. Triglyceride and high density lipoprotein cholesterol values in Soypro™ fed groups were similar compared to those of saline fed groups. Although further research is needed, these findings suggest that Soypro™ decreased the levels of low density lipoprotein cholesterol in high-fat diet-induced obesity and might partially inhibit the adipocyte differentiation through the suppression of a transcription factors peroxisome proliferator-activated receptor-γ_{2} and CCAAT/enhancer binding protein-α. Show more

Keywords: Soypro™, peroxisome proliferator-activated receptor-γ_{2}, CCAAT/enhancer binding protein-α, low density lipoprotein cholesterol

Citation: BioFactors, vol. 33, no. 1, pp. 49-60, 2008

Authors: Roomi, M.W. | Jariwalla, R.J. | Kalinovsky, T. | Roomi, N. | Niedzwiecki, A. | Rath, M.

Article Type: Research Article

Abstract: Influenza, a long-standing common infection, poses a serious health problem causing significant morbidity and mortality, and imposing substantial economic costs. To date there are no effective antiviral therapies. A unique nutrient mixture (NM), containing lysine, proline, ascorbic acid, green tea extract, N-acetyl cysteine and selenium among other micro nutrients, has been shown to exert a wide range of biochemical and pharmacological effects, among them anti-carcinogenic and anti-atherogenic activity both in vitro and …in vivo. In a previous study, NM was found to significantly inhibit influenza virus A associated neuraminidase enzyme as well as production of NP antigen in a dose-dependent manner. Influenza virus A not only infects pulmonary areas, but also manifests in extrapulmonary areas, which require basement membrane disruption by matrix metalloproteinases capable of degrading collagen type IV. This prompted us to study the effect of NM on cellular invasive parameters of virus-infected and non-infected MDCK and Vero cells. NM inhibited extracellular invasive parameters such as MMP-2 and MMP-9 secretion and Matrigel invasion. Results indicated that the relatively non-toxic nutrient mixture tested in this investigation has potential in influenza treatment by not only decreasing viral multiplication in infected cells but also by blocking the enzymatic degradation of the extracellular matrix. Show more

Keywords: Influenza A virus, nutrients, matrix metalloproteinases, Matrigel invasion, MDCK, Vero

Citation: BioFactors, vol. 33, no. 1, pp. 61-75, 2008

Authors: Takitani, Kimitaka | Miyazaki, Hiroshi | Takaya, Ryuzo | Tamai, Hiroshi

Article Type: Research Article

Abstract: The vitamin A status has been studied in type 2 diabetes and it is known that plasma retinol levels of patients with type 2 diabetes are elevated. However, the details of vitamin A metabolism in type 2 diabetes are unclear. β-Carotene exhibits biological activity as provitamin A and β-carotene 15,15'-monooxygenase (BCM) cleaves β-carotene to form retinal. We studied BCM gene expression in type 2 diabetic Goto-Kakizaki (GK) rats. BCM gene expression was analyzed in …the liver, intestine, and testis of 8- and 13-week-old GK rats and Wistar rats (control). The plasma and liver retinol levels were measured, and plasma retinol-binding protein (RBP) was detected. BCM gene expression in the liver, intestine and testis of GK rats was increased compared with that in controls. Plasma retinol levels and RBP levels were increased in GK rats, but hepatic retinol levels did not differ between GK rats and controls. BCM gene expression in the liver and intestine might affect retinol levels in type 2 diabetes. Conversion of β-carotene to retinal might be accelerated in the presence of insulin resistance status, so that plasma retinol levels are increased in type 2 diabetes. Show more

Keywords: β-carotene 15, 15'-monooxygenase, retinol, type 2 diabetes, retinol-binding protein, Goto-Kakizaki rats

Citation: BioFactors, vol. 33, no. 1, pp. 77-83, 2008