ABSTRACT
Maintenance of appropriate muscle mass is necessary for good quality of life as skeletal muscles play critical roles in locomotion, metabolic homeostasis, and thermogenesis. Polyamines are essential metabolites that regulate several important cellular functions. In C57BL6 mice who underwent sciatic nerve transection of the hind limb, compensatory muscle hypertrophy is enhanced by the administration of polyamines. However, the action mechanisms of polyamines in muscle hypertrophy remain unclear. Here, we isolated PA YEAST SC-1, a polyamine-rich Saccharomyces cerevisiae, from Baker's yeast. We examined whether PA YEAST SC-1 induces muscle hypertrophy and elucidated the underlying action mechanisms of polyamines and the active ingredients in PA YEAST SC-1 using C2C12 myotubes. PA YEAST SC-1 at 1 mg/mL increased myosin heavy chain expression in C2C12 myotubes. Mechanistically, PA YEAST SC-1 induced the activation of Akt/mechanistic target of rapamycin kinase/p70S6K signaling. Furthermore, PA YEAST SC-1 decreased the expression levels of the ubiquitin ligases, atrogin-1 and muscle RING finger-1, via forkhead box O1 phosphorylation. These findings suggest PA YEAST SC-1 as an effective food ingredient for the treatment of muscle hypertrophy.
Subject(s)
Quality of Life , Saccharomyces cerevisiae , Animals , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal , Muscle, Skeletal/metabolism , Hypertrophy/metabolism , Hypertrophy/pathology , Muscular Atrophy/metabolismABSTRACT
BACKGROUND: Lectins are proteins that bind specifically to the carbohydrate moiety of glyco-conjugates. Japanese mistletoe lectin given intragastrically affected cytokine gene expression in the mouse intestine. This study examines the actions of Lens culinaris agglutinin (LCA) on the gene expression of gluconeogenic enzymes in the intestine. RESULTS: The results of quantitative real-time reverse transcription-polymerase chain reaction indicated that LCA caused an up-regulation of the gene expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). This change was correlated with an increase in the expression of two transcription factors, HNF1α and HNF4α. Experiments using human colonic cancer Caco-2 cells demonstrated that LCA up-regulated the gene expression of G6Pase and PEPCK whereas insulin had the opposite effect. In addition, the observed up-regulation of HNF4α gene expression in the duodenum raises the possibility that the lectin promotes the colorectal cancer. CONCLUSION: Lentil beans should be cooked well to avoid unfavourable effects of LCA.
Subject(s)
Duodenum/enzymology , Gene Expression Regulation, Enzymologic , Gluconeogenesis , Lens Plant/metabolism , Plant Lectins/metabolism , Animals , Caco-2 Cells , Colorectal Neoplasms/etiology , Colorectal Neoplasms/metabolism , Duodenum/metabolism , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 1-alpha/metabolism , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plant Lectins/adverse effects , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
We conducted a preliminary investigation of the effects of visible light irradiation on plant extracts, and we observed a strong suppressive effect on interleukin (IL) 2 expression with the inhibition of c-Jun amino-terminal kinase (JNK) phosphorylation in Jurkat cells by visible light irradiation to ethanol extract from green soybeans (LIEGS). This effect was produced only by extracts from green soybeans (Glycine max) and not other-color soybeans. LIEGS suppressed the lipopolysaccharide-induced IL-6, IL-12 and TNF-α expression levels in human monocyte THP-1 cells in a concentration-dependent manner. LIEGS was applied for 8 weeks to NC/Nga mice. LIEGS suppressed the development of atopic dermatitis (AD)-like skin lesions and reduced the dermatitis scores of the mice. The light irradiation changed the various types of small-molecule compounds in extracts. Visible light irradiation to daidzein with chlorophyll b induced a novel oxidative product of daidzein. This product suppressed IL-2 expression in Jurkat cells.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/radiation effects , Glycine max/chemistry , Light , Plant Extracts/pharmacology , Plant Extracts/radiation effects , Animals , Anti-Inflammatory Agents/chemistry , Cytokines/metabolism , Dermatitis, Atopic/drug therapy , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Interleukin-2/biosynthesis , Jurkat Cells , MAP Kinase Signaling System/drug effects , Male , Mice , Plant Extracts/chemistryABSTRACT
The present study was performed to investigate the immune-modulating activities of extracts from green soybean (Glycine max) in a 2,4-toluene diisocyanate (TDI)-inducing guinea pig rhinitis model and a human trial study for allergic rhinitis. Hot water extracts of green soybean were chosen for animal experimentation on the basis of their ability to regulate the production of B cell-activating factor of the TNF family and a proliferation-inducing ligand in mouse spleen cells. Green soybean extracts significantly decreased the levels of ovalubumin (OVA)-specific IgE in mice and significantly suppressed the TDI-induced nasal mucosa secretion. An open-label human pilot study was performed on 16 subjects, using Japanese cedar pollinosis. The symptom scores for Japanese cedar pollinosis were better in the long-term green soybean extracts intake group than in the withdrawal short-term intake group. Green soybean extracts had great potential as an orally active immune modulator for the treatment of various allergic diseases.
Subject(s)
Glycine max/chemistry , Immunologic Factors/administration & dosage , Plant Extracts/administration & dosage , Rhinitis, Allergic, Seasonal/drug therapy , Rhinitis, Allergic, Seasonal/immunology , Adult , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Female , Guinea Pigs , Humans , Immunoglobulin E/immunology , Mice , Mice, Inbred BALB C , Pilot Projects , Pollen/immunology , Rhinitis, Allergic, Seasonal/genetics , Seeds/chemistry , Seeds/growth & development , Glycine max/growth & developmentABSTRACT
Many biological activities of green tea have been attributed to a major constituent, (minus;)-epigallocatechin gallate (EGCG). We previously reported that EGCG and an EGCG-free fraction derived from green tea modulated the gene expression of gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, in the mouse liver. EGCG is also known to affect the gene expression of enzymes related to lipid metabolism. However, it remains to be examined whether or not a constituent other than EGCG contributes to the change in gene expression of these enzymes. In this study, we prepared an EGCG-free water-soluble fraction (GT-W), and examined its effects on the hepatic gene expression of lipogenic enzymes in mice. The results of quantitative real-time PCR assays indicated that the dietary administration of GT-W for 4 weeks reduced the hepatic gene expression of lipogenic enzymes: fatty acid synthase, hydroxymethylglutaryl coenzyme A reductase, and acetyl-coenzyme A carboxylase alpha. Also, the gene expression of sterol regulatory element-binding transcription factor (Srebf)1 and/or Srebf2 was reduced, suggesting that the reduction of Srebfs contributed to the down-regulation of the lipogenic enzymes, since these transcription factors bind the promoter region to enhance their expression. The plasma levels of triglycerides and cholesterol were reduced with statistical significance in the group given a diet containing GT-W. These results suggest that in addition to EGCG, green tea contains some component(s) which may help to prevent arteriosclerosis and obesity.
Subject(s)
Catechin/analogs & derivatives , Lipid Metabolism/genetics , Liver/drug effects , Plant Extracts/pharmacology , Tea/chemistry , Animals , Arteriosclerosis/genetics , Arteriosclerosis/prevention & control , Blood Glucose/analysis , Catechin/metabolism , Catechin/pharmacology , Cholesterol/blood , Down-Regulation/drug effects , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Liver/enzymology , Male , Mice , Mice, Inbred BALB C , Obesity/genetics , Obesity/prevention & control , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plant Leaves/chemistry , Real-Time Polymerase Chain Reaction , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 2/genetics , Sterol Regulatory Element Binding Protein 2/metabolism , Triglycerides/bloodABSTRACT
Many biological activities of green tea have been attributed to a major constituent, (-)-epigallocatechin gallate (EGCG). We previously reported that EGCG and a catechin-rich green tea beverage modulated the gene expression of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the mouse liver. However, it remains to be examined whether or not a constituent other than EGCG contributes to the change in gene expression of these enzymes. In this study, we separated the hot water infusion of green tea leaves (GT) into an ethanol-soluble fraction (GT-E) and an EGCG-free water-soluble fraction (GT-W), and examined their effects using rat hepatoma H4IIE cells. The inclusion of GT, GT-E, and GT-W in the culture medium reduced the gene expression of G6Pase and PEPCK. GT-W caused a decrease in expression of the transcription factor HNF4α. Reduced levels of PEPCK and HNF4α proteins were demonstrated in the cells treated with GT-W. GT-W showed an activity similar to insulin, but different from EGCG. Administration of GT-W to mice for 4 weeks reduced the hepatic expression of G6Pase, PEPCK, and HNF4α. These results suggest that green tea contains some component(s) with insulin-like activity distinguishable from EGCG and that drinking green tea may help to prevent diabetes.
Subject(s)
Antioxidants/pharmacology , Carcinoma, Hepatocellular/enzymology , Gluconeogenesis/drug effects , Glucose-6-Phosphatase/metabolism , Liver/drug effects , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plant Extracts/pharmacology , Animals , Carcinoma, Hepatocellular/genetics , Catechin/pharmacology , Cell Line, Tumor , Diabetes Mellitus, Type 2/prevention & control , Gene Expression , Gluconeogenesis/genetics , Glucose-6-Phosphatase/genetics , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Insulin/metabolism , Liver/enzymology , Male , Mice , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Plant Leaves/chemistry , RNA, Messenger/analysis , Rats , Tea/chemistryABSTRACT
Tea has many beneficial effects. We have previously reported that green tea and a catechin-rich green tea beverage modulated the gene expression of the gluconeogenic enzymes glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the normal murine liver. In the present study, we examined the effects of oral administration of oolong tea on the hepatic expression of gluconeogenesis-related genes in the mouse. The intake of oolong tea for 4 weeks reduced the hepatic expression of G6Pase and PEPCK together with that of the transcription factor hepatocyte nuclear factor (HNF) 4α. When rat hepatoma H4IIE cells were incubated in the presence of oolong tea, the expression of these genes was repressed in accordance with the findings in vivo. The reduced protein expression of PEPCK and HNF4α was also demonstrated. We then fractionated oolong tea by sequential extraction with three organic solvents to give three fractions and the residual fraction (Fraction IV). In addition to organic fractions, Fraction IV, which was devoid of low-molecular-weight catechins such as (-)-epigallocatechin gallate (EGCG), had effects similar to those of oolong tea on H4IIE cells. Fraction IV repressed the gene expression of insulin-like growth factor binding protein 1, as insulin did. This activity was different from that of EGCG. The present findings suggest that drinking oolong tea may help to prevent diabetes and that oolong tea contains a component or components with insulin-like activity distinguishable from EGCG. Identification of such component(s) may open the way to developing a new drug for diabetes.
Subject(s)
Gene Expression Regulation, Enzymologic , Gluconeogenesis , Hypoglycemic Agents , Liver/enzymology , Tea , Animals , Cell Line, Tumor , Down-Regulation/drug effects , Drug Discovery , Gene Expression Regulation, Enzymologic/drug effects , Gluconeogenesis/drug effects , Gluconeogenesis/ethics , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacology , Insulin-Like Growth Factor Binding Protein 1/genetics , Insulin-Like Growth Factor Binding Protein 1/metabolism , Liver/metabolism , Male , Mice , Mice, Inbred BALB C , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , RNA, Messenger/metabolism , Rats , Tea/chemistry , Tea/metabolismABSTRACT
Green tea has been shown to have many beneficial health effects. We have previously reported that dietary (-)-epigallocatechin-3-O-gallate (EGCG), the major polyphenol in green tea, reduced gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the normal mouse liver. In the present study, we examined the effects of intragastrical administration of EGCG on the expression of gluconeogenesis-related genes in the mouse intestine. The results of experiments with the semi-quantitative reverse transcription-polymerase chain reaction indicated that EGCG at 0.6 mg/head caused a reduced expression of G6Pase, PEPCK, hepatocyte nuclear factor 1α (HNF1α), and HNF4α. Experiments using the quantitative real-time polymerase chain reaction confirmed these effects. We then examined the effects of EGCG using human colon carcinoma Caco-2 cells stimulated with dexamethasone and dibutyryl cAMP. The results were generally consistent with those from the experiments in vivo. The present findings suggest EGCG to contribute to the beneficial effects of green tea on diabetes, obesity, and cancer by modulating gene expression in the intestine.
Subject(s)
Antioxidants/pharmacology , Catechin/analogs & derivatives , Duodenum/drug effects , Duodenum/metabolism , Gene Expression Regulation/drug effects , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Acetylcysteine/pharmacology , Animals , Antioxidants/administration & dosage , Catechin/administration & dosage , Catechin/pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , MiceABSTRACT
Rat hepatoma H4IIE cells were stimulated with dexamethasone and dibutyryl cAMP to increase gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Inclusion of catechin-rich green tea beverage (GTB) in the culture medium reduced the up-regulation of these genes as well as that of hepatocyte nuclear factor 4 alpha (HNF4alpha) gene. GTB was fractionated into chloroform-soluble (Fraction I), ethyl acetatesoluble (Fraction II), methanol-soluble (Fraction III) and residual (Fraction IV) fractions. Fractions II and III containing catechins caused an attenuation of the up-regulated expression of these genes as well as the down-regulation of HNF4alpha gene expression. Fraction IV had a synergistic effect on the up-regulation by dexamethasone/dibutyryl cAMP of the PEPCK gene expression and upregulated HNF4alpha gene expression. These results suggest that GTB down-regulated the expression of the HNF4alpha gene to cause the down-regulated gene expression of gluconeogenic enzymes. One reason why GTB did not down-regulate hepatic PEPCK gene expression in previous animal experiments may be that the component(s) acting to up-regulate PEPCK gene expression was more effective in vivo than in cultured cells.
Subject(s)
Catechin/pharmacology , Gene Expression Regulation/drug effects , Gluconeogenesis/genetics , Glucose-6-Phosphatase/genetics , Liver Neoplasms, Experimental/enzymology , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Tea/chemistry , Animals , Base Sequence , Cell Line, Tumor , DNA Primers , Insulin/pharmacology , Liver Neoplasms, Experimental/genetics , Polymerase Chain Reaction , RatsABSTRACT
Mistletoe lectins have various biological activities including anti-cancer and immunomodulatory effects. We previously isolated a lectin (ML-J) from Japanese mistletoe. In the present study, we examined the effects of ML-J on cytokine gene expression in human colon adenocarcinoma Caco-2 cells and in the mouse intestine. The results of reverse transcription-polymerase chain reaction and quantitative real-time polymerase chain reaction indicated that ML-J caused an upregulation of the gene expression of the proinflammatory cytokines interleukin (IL)-8, tumor necrosis factor-alpha (TNF-alpha) and IL-6 in Caco-2 cells and TNF-alpha and IL-6 in the duodenum. This study provides the first example to show that a perorally administered plant lectin affects gene expression in the duodenum.
Subject(s)
Caco-2 Cells/drug effects , Cytokines , Gene Expression Regulation/drug effects , Intestines/drug effects , Mistletoe/chemistry , Plant Lectins/pharmacology , Animals , Caco-2 Cells/physiology , Cytokines/genetics , Cytokines/metabolism , Humans , Intestines/anatomy & histology , Intestines/physiology , MiceABSTRACT
Normal rats were given catechin-rich green tea as drinking fluid and the effects on hepatic gene expression were examined. The results of DNA microarray analysis and quantitative real-time reverse transcription-polymerase chain reaction indicated the down-regulated expression of genes for glucose-6-phosphatase (G6Pase) and fatty acid synthase, and the up-regulated expression of peroxisome proliferator activated receptor alpha in the rats given green tea for 4 weeks as compared with the water-given animals. One may expect anti-diabetic activity by catechin-rich green tea through its chronic down-regulatory effect on G6Pase expression.
Subject(s)
Catechin/pharmacology , Gene Expression Regulation , Liver/metabolism , Tea/metabolism , Animals , Fatty Acid Synthases/metabolism , Gluconeogenesis , Glucose-6-Phosphatase/metabolism , Male , Oligonucleotide Array Sequence Analysis , PPAR alpha/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Time FactorsABSTRACT
Green tea and its constituent (-)-epigallocatechin-3-O-gallate (EGCG) are known to have apoptosis-inducing activity on tumor cells including human leukemia HL-60 cells, providing an explanation for their anti-cancer effects. In the present study, we compared the sensitivity of undifferentiated cells and differentiated HL-60 cells with normal-like phenotypic characters. HL-60 cells treated with three differentiating agents were found to be resistant to EGCG-mediated apoptosis as compared with undifferentiated cells. Gene and protein expression of 67 kDa laminin receptor was down-regulated in differentiated HL-60 cells, suggesting its contribution to the difference in sensitivity in view of the fact that the receptor is a target of EGCG's action to induce apoptosis. The finding supports the view that EGCG induces apoptosis preferentially in cancer cells as compared with normal counterparts.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Catechin/analogs & derivatives , Cell Differentiation/drug effects , Tea , Catechin/pharmacology , Gene Expression Regulation, Leukemic/drug effects , HL-60 Cells , Humans , Receptors, Laminin/biosynthesisABSTRACT
The importin/exportin transport system provides the machinery involved in nucleocytoplasmic transport. Alterations of the levels of importins and exportins may play crucial roles in development, differentiation and transformation. Employing human leukaemia HL-60 cells, we and others have revealed the differentiation-associated changes in the protein and gene expression of these factors. The recent finding that a switch to the importin-alpha subtype triggers neural differentiation of embryonic stem cells underscores the importance of nucleocytoplasmic transport factors in cellular events. This review focuses on current research into the roles of importins and exportins in cell differentiation.