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Biomedical subjects

N Fujitsuka

Publications and source records attributed to N Fujitsuka.

At least 19 recordsLinked to original sources
PubMed2000

The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats.

The abundance of mRNAs for pyruvate dehydrogenase kinase (PDK) isoenzymes in four brain regions of young (10 wk) and aged (50 wk) rats was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNAs for PDK1, 2, and 4 were detected in all the regions examined. The level of PDK2 mRNA was the most abundant among the isoenzymes in all the brain regions when judged from the PCR cycles. The level of PDK1 mRNA was relatively high in cerebellum and cerebral cortex compared to medulla oblongata and hippocampus. Aging decreased the levels of mRNAs for PDK1 and 2 in cerebellum and increased the PDK2 mRNA in hippocampus and cerebral cortex. The level of PDK4 mRNA was not affected by aging. These results provide the first evidence suggesting that there is the regional difference in the abundance of mRNAs for PDK isoenzymes in rat brain and that the levels of mRNAs for the isoenzymes were affected by aging.

Aging↗
PubMed2000

The alpha-ketoisocaproate catabolism in human and rat livers.

Catabolism of alpha-ketoisocaproate in liver is mediated by cytosolic alpha-ketoisocaproate dioxygenase (KICD) and mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC). The latter is believed to be involved in the main pathway of the KIC catabolism. In the present study, we measured the activities of KICD and BCKDC in human and rat livers. The KICD activity in human liver was 0.9 mU/g tissue, which was 14.2% of the total activity of BCKDC, and that in rat liver was 4.2 mU/g tissue, which was only 1.0% of the total activity, suggesting that KICD in human liver plays a relatively important role in the alpha-ketoisocaproate catabolism. The KICD activity in human liver was significantly increased by cirrhosis. In rat liver, the enzyme activity was markedly increased by physical training and streptozotocin-induced diabetes, but not by feeding of a diet rich in branched-chain amino acids, although BCKDC activity was increased by feeding of the diet.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2000

Exercise training prevents maturation-induced decreases in insulin receptor substrate-1 and phosphatidylinositol 3-kinase in rat skeletal muscle.

We have previously reported that exercise training prevents a maturation-induced decrease in insulin sensitivity and suggested that an improvement of insulin sensitivity by exercise training was attributable, in part, to an increase in insulin-sensitive GLUT-4 on the skeletal muscle plasma membrane. In this study, we examined the effects of maturation and exercise training on the gene expression and protein content of the components of post-insulin receptor signal transduction in rat skeletal muscle. Rats aged 3 weeks were sedentary or trained by voluntary running through 4 or 27 weeks of age, and then the rats in both the sedentary and trained groups were killed and the gastrocnemius muscle was immediately removed for analysis of mRNA and protein content. The concentration of mRNA and protein for insulin receptor substrate-1 (IRS-1) in sedentary rats significantly decreased with maturation (49% and 63%, respectively, at age 27 weeks v age 4 weeks), but in trained rats they did not decrease with maturation. Although the level of phosphatidylinositol 3-kinase (PI 3-kinase) mRNA in sedentary rats was not altered with maturation, PI 3-kinase protein in sedentary rats significantly decreased with maturation (73% at 27 weeks v 4 weeks). However, PI 3-kinase protein in trained rats did not decrease with maturation. These results suggest that the prevention of maturation-induced decreases in the protein content of IRS-1 and PI 3-kinase is involved in the mechanisms responsible for the improvement of insulin sensitivity by exercise training, and exercise training may affect transcriptional regulation of the IRS-1 gene and posttranscriptional regulation of PI 3-kinase expression.

Animals↗
PubMed2000

Suppression of glycogen consumption during acute exercise by dietary branched-chain amino acids in rats.

The effects of a diet supplemented with branched-chain amino acids (BCAA; 4.8% or 6.2%) on BCAA catabolism and glycogen metabolism in rats were examined. Rats were fed a BCAA diet or control diet for 4 wk and part of the rats were subjected to exercise training during the experimental period. Feeding the BCAA diet increased serum BCAA concentrations and activity of the hepatic branched-chain alpha-keto acid dehydrogenase complex, the rate-limiting enzyme in the catabolism of BCAA, suggesting that dietary BCAA promotes BCAA catabolism. Although the serum glucose concentration and glycogen contents in the liver and gastrocnemius muscle of rested rats were not significantly affected by feeding of the BCAA diet, those in rats exhausted by acute exercise were 2-4-fold higher in rats fed the BCAA diet than in rats fed the control diet. The activity of pyruvate dehydrogenase complex in the liver and gastrocnemius muscle after acute exercise showed reverse trends; the complex activities (especially in liver) tended to be less in the BCAA diet group than in the control diet group. These results suggest that dietary BCAA spares glycogen stores in liver and skeletal muscle during exercise and that the decrease in pyruvate dehydrogenase complex activity in these tissues by dietary BCAA is involved in the mechanisms.

Amino Acids, Branched-Chain↗
PubMed1999

Insulin activation of pyruvate dehydrogenase complex is enhanced by exercise training.

We studied the effects of exercise training on the activity of the pyruvate dehydrogenase (PDH) complex in rat gastrocnemius muscle (experiment 1) and the response of the complex to glucose and insulin infusion (euglycemic clamp) in trained and sedentary rats (experiment 2). In experiment 1, half of the rats were randomly allocated as sedentary animals and the other half were trained by voluntary running exercise for 8 weeks. The total activity of the PDH complex was not affected by exercise training, and the activity state (proportion of the active form) of the PDH complex was decreased from 15.0%+/-2.4% to 7.5%+/-1.1% by exercise training. The activity of 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase ([3-HADH] an enzyme in beta-oxidation) was significantly higher in trained versus sedentary rats. In experiment 2, sedentary and trained rats were starved for 24 hours before performing the euglycemic clamp. Glucose and insulin infusion was performed by a euglycemic clamp (insulin infusion rate, 6 mU/kg/min) for 90 minutes. The PDH complex was inactivated to less than 1% in both sedentary and trained rats after 24 hours of starvation. The glucose infusion rate (GIR) during the euglycemic clamp was higher in trained versus sedentary rats. The euglycemic clamp resulted in activation of the PDH complex in both sedentary and trained rats, but the response of the PDH complex to the euglycemic clamp was significantly higher in trained rats (5.8%+/-0.5%) than in sedentary rats (2.9%+/-0.5%). These results suggest that exercise training promotes fatty acid oxidation in association with suppression of glucose oxidation in skeletal muscle under resting conditions, but increases the rate of carbohydrate oxidation when glucose flux into muscle cells is stimulated by insulin.

Animals↗
PubMed1998

Induction of nuclear respiratory factor-1 expression by an acute bout of exercise in rat muscle.

Nuclear respiratory factor 1 (NRF-1) is a regulatory factor of nuclear genes for respiratory subunits and for components of the mitochondrial transcription and replication machinery. This study investigated the effects of an acute bout of aerobic exercise on the postexercise expression of mRNA for NRF-1 and RNA moiety of endonuclease for mitochondrial RNA processing (MRP-RNA) in soleus muscle of 5 days-trained and untrained rats. In the trained group, rats were run on a motor-driven treadmill at a speed of 25 m/min for 90 min/day for 5 days. On the final day, rats were run by the same procedures and were sacrificed at various postexercise time points (0.5, 3, 6, and 24 h). The basal level of cytochrome oxidase activity was increased by the training, which was associated with the increase in the expression of mRNAs for subunit VIc and III of the enzyme. The NRF-1 mRNA expression was transiently increased by approximately 35% at the time point of 6 h after exercise, although the basal level of the expression was not altered by training. A similar transient increase (approximately 50%) in NRF-1 expression by the acute bout of exercise was also observed in untrained rats. In contrast to the NRF-1 expression, the basal level of MRP-RNA abundance was not altered by 5 days training and was not affected by the single exercise bout in either 5 days-trained or untrained rats. These results suggest that the postexercise increase in NRF-1 mRNA expression in rat skeletal muscle may be an early response to endurance exercise for an enhancement of the mitochondrial oxidative capacity.

Animals↗
PubMed1998

Intramembrane structure of the sensory axon terminals in bullfrog muscle spindles.

Much physiologic and morphologic research has been done into the sensory mechanism of the frog muscle spindle. However, no freeze-fracture study has described in detail the shape and intramembrane structure of the nonmyelinated sensory axon terminals of the frog muscle spindle. In this study, muscle spindles were isolated from the red part of bullfrog semitendinous muscles. Chemically fixed spindles were subjected to freeze fracturing. The sensory axon endings were reconstructed, and the size and density of intramembrane particles (IMPs) were measured along the sensory nerve endings. The axon terminals had four distinctive parts: parent trunks (>0.5 microm in diameter), primary branches (0.15-0.5 microm), terminal branches (<0.1 pm), and varicosities (0.02-0.5 microm). IMPs ranged from 5 nm to 21 nm in diameter and were present in the intramembrane space of the plasma membrane all throughout the nonmyelinated sensory nerve endings. Mean IMP sizes in the protoplasmic face (PF) and the external face (EF), respectively, were 8.1 nm and 8.4 nm in the parent trunks, 8.8 nm and 8.8 nm in the primary branches, 9.4 nm and 9.0 nm in the varicosities, and 8.7 nm and 8.7 nm in the terminal branches. Mean IMP size in the PF was smallest in the parent trunk and largest in the varicosity. Mean IMP densities (numbers of IMPs per microm2) in the PF and the EF, respectively, were 2,500 and 700 in the parent trunks, 2,200 and 500 in the primary branches, 1,700 and 400 in the varicosities, and 1,000 and 300 in the terminal branches. Density decreased with the tapering of the axon terminal, with IMPs distributed evenly in the PF and the EF. The characteristic intramembrane structure of sensory nerve endings is discussed.

Animals↗
PubMed1998

Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine-induced cecum and proximal colon tumors in rats.

Maltitol is fermented in the colon due to only partial hydrolysis in the small intestine. In the present study, we examined effects of dietary maltitol on dimethylhydrazine-induced intestinal tumor in rats. In experiment 1, rats were fed a fiber-free diet or diets supplemented with 1 or 5 g/100 g maltitol for 27 wk. Each group of rats was injected with dimethylhydrazine or vehicle alone for the first 14 wk of the experimental period. Maltitol supplementation at 1 g/100 g of the diet significantly reduced tumor incidence in the cecum and the 5% supplement reduced tumor incidence in both the cecum and proximal colon in dimethylhydrazine-treated rats. In experiment 2, we investigated the effect of the 1 g/100 g maltitol diet on the short chain fatty acid concentrations in cecal contents of placebo and dimethylhydrazine-treated rats. Intake of the 1 g/100 g maltitol diet doubled (P < 0.05) the concentration of butyrate but did not affect acetate or propionate in the cecal contents. These results suggest that dietary maltitol has a protective effect against dimethylhydrazine-induced tumors in rat cecum and proximal colon and that butyrate produced by bacterial fermentation of maltitol in the cecum may be involved in the protection.

1,2-Dimethylhydrazine↗
PubMed1997

Gender difference in regulation of branched-chain amino acid catabolism.

Regulation of the activity state of the hepatic branched-chain 2-oxo acid dehydrogenase (BCODH) complex during the light-dark cycle differs markedly in male and female rats. Female rats exhibit a profound diurnal rhythm in the activity state of the complex that is not observed in male rats. Regardless of gender, most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats at the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Gonadectomy prevented the diurnal rhythm in females but was without effect in males, indicating that female sex hormones are required for this gender difference in regulation of the BCODH complex. Changes in levels of branched-chain 2-oxo acids, known regulators of BCODH kinase, do not seem to be involved; rather, an increase in BCODH kinase activity occurring between morning and evening is responsible for inactivation of the BCODH complex in female rats. The increase in kinase activity is due to an increase in the amount of kinase protein associated with the BCODH complex. Thus a marked diurnal variation in the amount of BCODH kinase and therefore its activity results in large swings in the activity state of the liver BCODH complex in female rats. This study provides the first evidence for a gender-specific difference in the regulation of branched-chain amino acid catabolism.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1997

Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA dehydrogenase in sand rat (Psammomys obesus).

The sand rat (Psammomys obesus) is an animal model for non-insulin dependent diabetes mellitus, which is induced by a regular chow diet. The total activity of liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats. These metabolic conditions may be related to the predisposition of the animals towards diabetes. Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver pyruvate dehydrogenase complex and in increasing the activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Effects of aging on the activities of pyruvate dehydrogenase complex and its kinase in rat heart.

Effects of aging on the activities of heart pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase were examined using 7, 35 and 60 wk old rats. Aging did not affect the total activity of pyruvate dehydrogenase complex but decreased the activity state (percentage of active form) of the complex in rats under the fed condition (52%, 36% and 26% for 7, 35 and 60 wk old rats, respectively). This decrease in the complex activity with aging was suggested to be associated with an age-related decrease in the blood glucose disposal. Starvation for 24 h decreased the activity state to less than 3% in all of the age groups. The activity of pyruvate dehydrogenase kinase associated with the complex was not related to the alteration in the activity state of the complex; the kinase activity was slightly lower in 60 wk old rats than in the younger rats under the fed condition and activation of the kinase by starvation was greater in the younger rats. The mechanism for the decrease in activity of pyruvate dehydrogenase complex was discussed on the basis of glucose and fatty acid utilization of heart muscle cells.

Aging↗
PubMed1997

Enlargement glycogen store in rat liver and muscle by fructose-diet intake and exercise training.

This study investigated the effect of long-term intake of a fructose diet and exercise training on glycogen content in liver and skeletal muscle in female rats. Thirty-six rats (8 wk old) were divided into two dietary groups and were fed with a control (chow) diet or fructose diet (containing 20%) fructose) for 12 wk. During this period, one-half of the rats in each dietary group were trained by using a motor-driven treadmill (running speed of 25 m/min and duration of 90 min/day, 5 days/wk). The liver glycogen was increased by intake of a fructose diet and exercise training, and the content was in the following order: control-diet and sedentary rats < fructose-diet and sedentary rats < or = control-diet and trained rats < fructose-diet and trained rats in the ratio of 1:3.4:3.6:5.0. The glycogen content in gastrocnemius muscle showed the same trend as that in liver; the ratio was 1:1.3:1.3:1.6. These results indicate that both long-term intake of the fructose diet and exercise training synergistically increased glycogen in both tissues.

Animals↗
PubMed1997

[Sairei-to may inhibit the synthesis of endothelin-1 in nephritic glomeruli].

In order to clarify the antinephritic mechanisms of Sairei-to (TJ-114), its effects on the synthesis and expression of endothelin-1 were evaluated in rats with anti-glomerular basement membrane (GBM) nephritis. TJ-114 was administered orally once daily from the 20th day after anti-GBM serum injection and was continued throughout the experiment. TJ-114 prevented proteinuria and histopathological changes in the glomeruli of nephritic rats. TJ-114 inhibited elevation of the endothelin-1 concentration in the supernatant from cultured glomeruli of nephritic rats and the endothelin-1 positive area in the glomeruli. TJ-114 inhibited the elevation of systolic blood pressure and the number of proliferating cell nuclear antigen (PCNA)-positive cells per glomeruli. We also found that the constitutive Kampo medicine in TJ-114, Gorei-san (TJ-17), inhibited the synthesis and expression of endothelin-1. In addition, the constitutive herbs TJ-17, alismatis rhizoma (Japanese name "Takusha") and hoelen (Japanese name "Bukuryou") inhibited the synthesis and expression of endothelin-1. These results indicate that the antinephritic actions of TJ-114 may be due partially to the inhibition of endothelin-1 synthesis in the glomeruli.

Animals↗
PubMed1997

[Protective effect of onpi-to (TJ-8117) on the expression of apoptosis in 5/6 nephrectomized rats].

The present study was designed to clarify the effects of TJ-8117 on apoptosis in the glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/day), captopril (50 mg/kg/day) and nicardipine (50 mg/kg/day) were administered as drinking water from the 56th day after renal ablation, and continued throughout the experiment. All rats were sacrificed at 13 weeks and renal tissues were removed to quantify histopathological and apoptotic parameters in glomeruli. TJ-8117 inhibited proteinuria, matrix index and decrease in the number of total cells in glomeruli of nephrectomized rats. In addition, the increase in apoptotic body and DNA fragmentation was significantly inhibited in the TJ-8117-treated group. Captopril and nicardipine failed to inhibit both parameters. In 400 mg/kg of the TJ-8117 treated group, the number of Bcl -2 positive cells in the glomeruli was elevated compared with the 5/6 nephrectomized control group. In addition, the number of Bax positive cells in the TJ-8117 group was significantly suppressed in a dose-dependent manner. These results suggest that TJ-8117 may inhibit apoptosis in the late stage of this model by suppressing matrix accumulation and progression of glomerulosclerosis. The apoptosis-preventing effect may be mediated by decreased expression of Bax in the glomerular cells.

Animals↗
PubMed1997

[Effects of onpi-to (TJ-8117) and (-)epicatechin-3-O-gallate on the proliferating changes in glomeruli of 5/6 nephrectomized rats].

Onpi-to (TJ-8117) is a herbal medicine composed of five crude drugs (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber). Our previous experiments have demonstrated that TJ-8117 suppressed the development of glomerulosclerosis and retarded the deterioration of renal function in 5/6 nephrectomised rats. In the present study, the effects of TJ-8117 and (-)Epicatechin-3-O-gallate (ECG), which is a component of Rhei Rhizoma, on glomerular cell proliferation, extracellular matrix accumulation and glomerular hypertrophy were investigated in 5/6 nephrectomized rats. Male Wistar rats (170-180 g) were subjected to 5/6 nephrectomy, and TJ-8117 (0.32%, 0.64%) or angiotensin-converting enzyme inhibitor, captopril (CAP 0.08%) was administered daily by mixing in normal chow and ECG (2 mg, 8 mg/100 ml) by drinking water from the day after 5/6 nephrectomy. Following 5/6 nephrectomy, glomerular cell poliferation was increased and reached a maximum at 1 week in the untreated control rats, but was suppressed significantly at 1 and 2 weeks after treatment with TJ-8117 and at only 1 week after treatment with CAP. Extracellular matrix accumulation was detected after 1 week and increased gradually until 4 weeks in the control rats, whereas it was significantly inhibited in both the TJ-8117- and CAP-treated rats. In addition, immunohistochemistry revealed that TJ-8117 significantly inhibited the increase of fibronectin, and tended to reduce type I and type IV collagen at 4 weeks. Furthermore, TJ-8117 suppressed glomerular hypertrophy at 4 weeks. Systolic blood pressure (SBP) and urinary protein excretion (UP) were higher in the control rats than sham-operated rats. TJ-8117 prevented this increase of SBP and UP at 1 week. ECG also suppressed glomerular cell proliferation and the increase of SBP and UP at 1 week after 5/6 nephrectomy. These findings suggest that ECG was one of active components of TJ-8117. These results suggest that TJ-8117 suppressed proliferating changes in glomeruli at an early stage in 5/6 nephrectomized rats, and inhibited the development of glomerulosclerosis.

Animals↗
PubMed1996

The valine catabolic pathway in human liver: effect of cirrhosis on enzyme activities.

The activities of key enzymes in the valine catabolic pathway--branched-chain aminotransferase, branched-chain alpha-keto acid dehydrogenase complex, methacrylyl (MC)-coenzyme A (CoA) hydratase (crotonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase--were measured in normal and cirrhotic human livers. Unlike rat liver, which does not contain branched-chain aminotransferase, the aminotransferase activity in the normal liver was measurable and is increased somewhat in cirrhosis of the human liver. The total activity of branched-chain alpha-keto acid dehydrogenase complex in the normal human liver was approximately 1% of that in rat liver, and 20% to 30% of the complex was in the active form in both normal and cirrhotic livers. Only the actual activity of the enzyme was significantly decreased by cirrhosis. These results suggest that human liver is less active than rat liver in the catabolism of branched-chain amino and alpha-keto acids. Activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver were very high compared with that of branched-chain alpha-keto acid dehydrogenase complex, suggesting an important role for these enzymes in catabolism of a potentially toxic compound, MC-CoA, formed as an intermediate in the catabolism of valine and isobutyrate. Cirrhosis resulted in a significant decrease in HIB-CoA hydrolase activity but had no effect on the citrate synthase activity, suggesting that the decrease in HIB-CoA hydrolase activity does not reflect a general decrease in mitochondria but that it may contribute to cellular damage that culminates in liver failure.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

Glycogen depletion of the intrafusal fibers in a mouse muscle spindle during prolonged swimming.

This study investigated the recruitment of different types of intrafusal fibers during prolonged swimming at 60-75% of VO2max. We used 56 male adult mice and examined depletion of glycogen in soleus (Sol) and extensor digitorum longus (EDL) muscle spindles by visual inspection and a newly developed optical scanning method. More than 80% of all spindles from six mice consisted of four fibers: one type I nuclear bag (bag1) fiber, one type II nuclear bag (bag2) fiber, and two nuclear chain fibers. Glycogen content was estimated in muscle fibers from groups of six mice that had rested or swum for either 0.5, 1, 2, 4, or 8 h. The optical scanning intensity of periodic acid Schiff (PAS)-stained sections was correlated with their biochemically determined glycogen content (r = 0.93). Both methods showed fundamentally the same result: each type of intrafusal fiber has its own typical recruitment pattern during exercise. In the initial phase (0-0.5 h), glycogen depletion was largest in nuclear bag1 fibers and insignificant in the bag2 and chain fibers. With the bag1 fibers having become fatigued, nuclear bag2 fibers mainly took over during the middle phase (2-4 h). During the last phase (4-8 h), only the glycogen content of chain fibers decreased significantly (4-8 h). There were significant correlations between the recruitment pattern of bag1 and extrafusal type I fibers in both Sol and EDL, between nuclear bag2 and type IIa fibers in Sol, and between nuclear chain and type IIb fibers in EDL. This suggests that, during moderately intense exercise, glycogen depletion occurs first in the slow, then the intermediate, and, finally, the fast intrafusal fibers.

Animals↗