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K Suruga

Publications and source records attributed to K Suruga.

At least 19 recordsLinked to original sources
PubMed2005

Enhancing effect of taurine on CYP7A1 mRNA expression in Hep G2 cells.

Taurine has been reported to enhance cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in animal models. However, no in vitro studies of this effect have been reported. The Hep G2 human hepatoma cell line has been recognized as a good model for studying the regulation of human CYP7A1. This work characterizes the effects of taurine on CYP7A1 mRNA levels of Hep G2 cells in a dose- and time-dependent manner. In the dose-dependent experiment, Hep G2 cells were treated with 0, 2, 10 or 20 mM taurine in the presence or absence of cholesterol 0.2 mM for 48 h. In the time-dependent experiment, Hep G2 cells were treated with 0 or 20 mM taurine for 4, 24 and 48 h with and without cholesterol 0.2 mM. Our data revealed that taurine showed time- and dose-response effects on CYP7A1 mRNA levels in Hep G2 cells. However, glycine - a structural analogue of taurine - did not have an effect on CYP7A1 gene expression. These results show that, in agreement to previous studies on animal models, taurine induces the mRNA levels of CYP7A1 in Hep G2 cells, which could enhance cholesterol conversion into bile acids. Also, Hep G2 cell line may be an appropriate model to study the effects of taurine on human cholesterol metabolism.

Animals↗
PubMed2001

Modulation of the expression of peroxisome proliferator-activated receptor-dependent genes through disproportional expression of two subtypes in the small intestine.

We have reported that dietary long-chain triacylglycerols (LCT) enhance the transcription of cellular retinol-binding protein, the type II (CRBPII) gene, and the liver-type fatty acid-binding protein (L-FABP) gene in the small intestine. Because the cis elements on the CRBPII gene consisting of two AGGTCA motifs separated by a single nucleotide are known to bind not only the 9-cis-retinoic acid receptor (RXR) homodimer, but also the peroxisome proliferator-activated receptor (PPAR)-RXR heterodimer, it has been implicated that the unsaturated long-chain fatty acids, as the ligands of the PPAR, might activate the transcription of the CRBPII gene, thereby making use of the RXR-response elements (RXRE and RE3) as the PPAR-response element (PPRE). In this study, we found that the PPARalpha mRNA level in the rat jejunum was elevated by dietary fat, whereas the PPARdelta mRNA level was reduced under this condition. Electrophoretic mobility-shift assay revealed that both PPARalpha-RXRalpha and PPARdelta-RXRalpha heterodimers, specifically and in a dose-dependent manner, bound to the two PPRE-like elements of the rat CRBPII gene as well as the known PPREs in the L-FABP and acyl-CoA oxidase genes. The binding of the PPARalpha-RXRalpha heterodimer to the CRBPII-RXRE, the CRBPII-RE3, and the PPREs of L-FABP, HMG-CoA synthase, and acyl-CoA oxidase was gradually diminished by the addition of increasing amounts of PPARdelta. The binding of the PPARdelta-RXRalpha heterodimer to CRBPII-RXRE, CRBPII-RE3, and other PPREs was also gradually reduced by the addition of increasing amounts of PPARalpha. Using Escherichia coli-expressed RXRalpha, we showed that the mutual competition for RXRalpha with PPARalpha and PPARdelta occurred at the protein level. These results suggest that the transcriptions of CRBPII, L-FABP, and the other PPAR-dependent genes in the small intestine may be coordinately regulated by the disproportional expression of PPARalpha and PPARdelta.

Animals↗
PubMed2001

The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine.

In this study, we found that the mRNA level of peroxisome proliferator-activated receptor (PPAR) alpha, but not of PPARdelta, was elevated in the jejunum during the postnatal development of the rat. Moreover, we found that the expressions of PPAR-dependent genes, such as acyl-CoA oxidase, L-FABP, and I-FABP, were also increased during the postnatal development of the small intestine. Electrophoretic mobility shift assay revealed that both the PPARalpha-9-cis-retinoic acid receptor alpha (RXRalpha) heterodimer and the PPARdelta-RXRalpha heterodimer bound to the peroxisome proliferator response element (PPRE) of acyl-CoA oxidase and L-FABP genes. The binding of the PPARalpha-RXRalpha heterodimer to the PPREs of the various genes was enhanced by the addition of PPARalpha, with a concomitant reduction of the binding of PPARdelta-RXRalpha to the PPREs. Furthermore, the binding activity of PPARalpha-RXRalpha, but not PPARdelta-RXRalpha, to the PPREs was enhanced by the addition of a PPAR ligand, WY14,643. The GAL4-PPAR-chimera reporter assay showed that WY14,643 transactivated the reporter gene through action of PPARalpha, but not through PPARdelta, in Caco-2 cells. Furthermore, oral administration of a PPAR ligand, clofibrate, during 3 consecutive days of the weanling period caused a parallel increase in the mRNA levels of these PPAR-dependent genes. These results suggest that acyl-CoA oxidase, L-FABP and the other PPAR-dependent genes in the small intestine may be coordinately modulated during postnatal development by the disproportional expression of PPARalpha over PPARdelta.

Acyl-CoA Oxidase↗
PubMed2000

Regulation of vitamin A metabolism-related gene expression.

Cellular retinol-binding protein, type II (CRBPII) is abundantly expressed in the small intestinal epithelial cells and plays a pivotal role in intestinal absorption and metabolism of retinol and beta-carotene. In the 5'-flanking region of rat CRBPII gene, two DR-1 type elements which consist of a direct repeat of the AGGTCA-like motif spaced by a single nucleotide have been identified as putative binding sites for a heterodimer of peroxisome proliferator-activated receptor (PPAR) and retinoid X-receptor (RXR). We found that CRBPII levels were elevated in the residual jejunal segment of rats subjected to jejunal bypass operation, where a concomitant increase in the apoprotein B levels occurred. This result suggested that CRBPII expression was enhanced by a condition where fat absorption was stimulated. Indeed, dietary fat (especially unsaturated fatty acids) has been shown to induce CRBPII gene expression in the jejunum. Nuclear run-on assays revealed that this increase of CRBPII mRNA levels by a high-fat diet was the result of the induction of the gene transcription through the rise in PPARalpha expression level as well as the increase in its ligand levels. Electrophoretic mobility shift assay using the DR-1 type cis-elements of CRBP II gene showed that PPARalpha-RXRalpha heterodimer was capable of binding to these elements, and that nuclear extracts from the jejunum of rats fed the high-fat diet gave greater density of retarded bands than those of rats fed a fat-free diet. We also found that the expression of PPARdelta was rather reduced by dietary fat. Thus, CRBPII gene expression is regulated predominantly by dietary fatty acids.

Animals↗
PubMed2000

Structure of cytochrome c6 from the red alga Porphyra yezoensis at 1. 57 A resolution.

The crystal structure of cytochrome c(6) from the red alga Porphyra yezoensis has been determined at 1.57 A resolution. The crystal is tetragonal and belongs to space group P4(3)2(1)2, with unit-cell parameters a = b = 49.26 (3), c = 83.45 (4) A and one molecule per asymmetric unit. The structure was solved by the molecular-replacement method and refined with X-PLOR to an R factor of 19.9% and a free R factor of 25.4%. The overall structure of cytochrome c(6) follows the topology of class I c-type cytochromes in which the heme prosthetic group covalently binds to Cys14 and Cys17, and the iron has an octahedral coordination with His18 and Met58 as the axial ligands. The sequence and the structure of the eukaryotic red algal cytochrome c(6) are very similar to those of a prokaryotic cyanobacterial cytochrome c(6) rather than those of eukaryotic green algal c(6) cytochromes.

Amino Acid Sequence↗
PubMed1999

Transcriptional regulation of cellular retinol-binding protein, type II gene expression in small intestine by dietary fat.

We have previously demonstrated that dietary fat, especially unsaturated fatty acids, induces cellular retinol-binding protein, type II (CRBPII) gene expression in rat jejunum. In the present study, we showed that feeding a high-fat diet caused parallel increases in jejunal CRBPII mRNA and CRBPII pre-mRNA levels. Nuclear run-on assay also revealed that this increase of CRBPII mRNA level by high-fat diet was, at least in part, triggered at a transcription level. Moreover, peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA level was also increased in the jejunum by high-fat diet. Gel shift assay showed that the binding activity of rat jejunal nuclear protein to the nuclear receptor response elements located in the rat CRBPII gene (RXRE and RE3) was greater in rats fed high-fat diet than in those fed fat-free diet and were enhanced by addition of bacterially expressed PPARalpha protein. Also PPARalpha-retinoid X receptor alpha (RXRalpha) heterodimer was capable of binding to the CRBPII-RXRE and RE3 elements and these binding activities were enhanced by addition of some PPARalpha ligands in the gel shift assay. Taken together, these studies suggest that dietary fatty acids may lead to induction of CRBPII gene transcription through increases of PPARalpha as well as its ligand levels.

Animals↗
PubMed1999

Regulation of cellular retinol-binding protein type II gene expression by arachidonic acid analogue and 9-cis retinoic acid in caco-2 cells.

We previously showed that unsaturated fatty acids induced gene expression of cellular retinol-binding protein type II (CRBPII) in rat jejunum [Suruga, K., Suzuki, R., Goda, T. and Takase, S. (1995) J. Nutr. 125, 2039-2044]. In the present study, we investigated this induction mechanism(s) using the human intestinal Caco-2 cell line. The postconfluent mature Caco-2 cells were maintained in serum-free medium containing arachidonic acid or its analogue, 5,8,11, 14-eicosatetraynoic acid (ETYA). Northern blot analysis showed that these compounds induced CRBPII mRNA levels to rise and that this induction was more effective when combined with 9-cis retinoic acid. This effect was independent of cycloheximide and inhibited by actinomycin D. Nuclear run-on assays confirmed that the ETYA and 9-cis retinoic acid-induced increase of CRBPII mRNA levels was due to an increased rate of transcription of its gene. In Caco-2 cells, the transcripts of peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor alpha (RXRalpha), which were activated by their ligands ETYA and 9-cis retinoic acid, respectively, were coexpressed. The gel shift study using rat CRBPII gene nuclear receptor response elements (RXRE, RE2, RE3) revealed that several forms of nuclear proteins from Caco-2 cells specifically bound to these elements. Some of these protein/DNA complexes reacted to both anti-RXRalpha and anti-PPAR antibodies. In addition, in-vitro synthesized RXRalpha and PPARalpha cooperatively bound to these elements as a heterodimer and these binding activities were enhanced by addition of ETYA or arachidonic acid but not by addition of 9-cis retinoic acid. These studies suggest that fatty acid or its analogue may regulate CRBPII gene expression through PPAR/RXR heterodimer bound to the nuclear receptor response element(s) of the CRBPII genes.

Alitretinoin↗
PubMed1999

Developmental induction and villus-crypt distribution of retinol esterifying enzyme activities in chick duodenum.

Retinol absorbed and generated from dietary beta-carotene can be esterified by retinol esterifying enzyme(s) in intestinal absorptive cells. In this study, we observed the developmental changes and villus-crypt distribution of the activities of two retinol esterifying enzymes (lecithin-retinol acyltransferase (LRAT); and acyl-CoA-retinol acyltransferase (ARAT) in chick duodenum) to seek the possibility that these enzymes play distinct roles in retinol absorption and metabolism. Intestinal LRAT activity was barely expressed in embryonic stages until 2-3 d before hatching, when its activity becomes detectable; thereafter it abruptly increased to the maximal level at the third day of the posthatch period. In contrast, ARAT activity was present in the duodenum at the earliest stage examined, the 15th day of embryogenesis, and was elevated to the maximal level 3-4 d after hatching. An assay of LRAT and ARAT activities along the villus-crypt axis of the duodenum by a cryostat sectioning technique revealed that between the day of hatching and 1 d posthatch, an abrupt induction of LRAT activity occurred only in the villus region of the duodenum, where a coordinated induction of cellular retinol-binding protein, type II (CRBPII), was observed. In contrast, the rise in ARAT activity observed around the hatching period occurred at the broader portions of the villi including the area of villus-crypt junction. These observations in the developmental changes and distribution of LRAT and ARAT activities suggest that LRAT activity but not ARAT activity is closely related to the induction of CRBPII in the duodenum of developing chicks.

Acyltransferases↗
PubMed1998

Peroxisome proliferator enhances gene expression of cellular retinol-binding protein, type II in Caco-2 cells.

Both the mRNA and protein of cellular retinol-binding protein, type two (CRBP(II)) are induced in rat intestine by high fat (corn oil) diet (Biochim. Biophys. Acta 1200, 34-40, 1994) as well as by dietary unsaturated long-chain fatty acids (J. Nutr. 125, 2039-2044, 1995). To gain an insight into the mechanism for this induction, we investigated whether CRBP(II) gene was activated by exposure of the human intestinal cell line, Caco-2 to a peroxisome proliferator (clofibric acid) and/or 9-cis retinoic acid. Northern blot hybridization revealed that Caco-2 cells endogenously expressed the mRNAs of peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor alpha (RXRalpha). The expression of the genes encoding CRBP(II), PPARalpha, and RXRalpha increased progressively during differentiation of Caco-2 cells. The cells exposed to 100 microM clofibric acid exhibited 70% greater CRBP(II) mRNA and the exposure of the cells to 100 microM clofibric acid in combination with 100 microM 9-cis retinoic acid exhibited 130% greater CRBP(II) mRNA level, indicating that the effect of the combination of them was additive. Neither PPARalpha mRNA nor RXRalpha mRNA level was enhanced by clofibric acid. In conclusion, our data suggested that the CRBP(II) gene expression may be enhanced by an activation of PPARalpha-RXRalpha heterodimer through some putative metabolite(s) formed via fatty acid-related metabolic pathway in the clofibrc acid-treated cells.

Alitretinoin↗
PubMed1998

Dietary fatty acids are possible key determinants of cellular retinol-binding protein II gene expression.

We previously found that dietary unsaturated fatty acids increase cellular retinol-binding protein type II (CRBP II) mRNA and its protein levels in rat jejunum. To obtain insight into mechanisms for its gene induction, we investigated the effect of depletion of dietary fat on CRBP II mRNA levels and we further examined whether dietary retinol is necessary for dietary fat-induced CRBP II gene expression. Feeding the fat-free diet, which contained a sufficient amount of vitamin A, repressed CRBP II mRNA accumulation by 50% within 1 day, and this low level was sustained over the next 9 days. Parallel to the decreased CRBP II mRNA level, the peroxisomal proliferator-activated receptor-alpha (PPAR-alpha) mRNA level in rat jejunum was decreased by long-term (7 days) feeding of an isocaloric low-fat diet compared with the control. Oral administration of corn oil in the animals fed vitamin A-free diet elicited approximately threefold accumulation of CRBP II mRNA within 6 h. However, the administration of 9-cis-retinoic acid brought about no accumulation of CRBP II mRNA. Even when rats were vitamin A-deficient, oral administration of corn oil, but not 9-cis-retinoic acid, caused an increase in jejunal CRBP II mRNA level. These results suggest that CRBP II gene expression in rat jejunum may be regulated predominantly by dietary fatty acids but little by dietary retinoids.

Alitretinoin↗
PubMed1997

Cloning of chick cellular retinol-binding protein, type II and comparison to that of some mammals: expression of the gene at different developmental stages, and possible involvement of RXRs and PPAR.

We cloned chick cellular retinol-binding protein, type two (CRBP II) cDNA and compared it with those of some mammals. The deduced amino acid sequence showed that chick CRBP II was one amino acid greater in size than those of mammals, and the nucleotide sequence of chick CRBP II shared 72%-75% similarity with those of mammals. RNA blot hybridization analysis showed that CRBP II transcript of 0.7 kb was first detected in the duodenum of day-18 embryonic chick, and exhibited a rapid increase during 24 hr around the hatching. Northern blot hybridization also revealed that the transcripts of two types of retinoid X receptors (RXR alpha and RXR gamma) and peroxisome proliferator-activated receptor (PPAR) were expressed in the chick duodenum at hatching. The organ culture of day 16 embryonic chick duodenum showed that the addition of 9-cis retinoic acid in the medium caused a significant increase in CRBP II mRNA levels. In addition, arachidonic acid, from which putative ligands for PPAR were supposed to be generated, was accumulated around hatching in the duodenum. The results may suggest that the abrupt increase of the CRBP II gene expression in the chick duodenum around hatching may be related with RXRs and/or PPAR.

Animals↗
PubMed1997

Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation.

We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil-fed rats were significantly lower (P < 0.05) than those of olive oil- and beef tallow-fed groups. The product of [(volume of individual adipocytes) x (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor alpha, adipocyte P2 and adipsin, was significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil-fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.

Adipocytes↗
PubMed1996

Relationship between perinatal appearance of cellular retinol-binding protein, type II and retinal reductase activity in chick liver.

To explore a role of the transiently appearing cellular retinol-binding protein, type II (CRBP(II)) in perinatal chick liver, we have examined whether the relationships exist among the perinatal changes in hepatic CRBP(II) protein and mRNA levels, retinal reductase activity and beta-carotene levels in liver and serum. Northern blot analysis for hepatic CRBP(II) revealed a transient expression of CRBP(II) mRNA around hatching. The protein of CRBP(II) was also expressed transiently and the highest levels of CRBP(II) were found in the livers 1-3 days after birth. The retinal reductase activity was very low at embryonic age, but its activity rapidly rose at hatching, peaking at 1 day after birth, followed by a gradual decrease to a lower level in 7-day-old chicks. This perinatal pattern of the retinal reductase activities was similar to the pattern of transient appearance of the hepatic CRBP(II), and was also paralleled to the developmental changes in serum and liver beta-carotene concentrations. These findings suggest that hepatic CRBP(II) transiently appearing during the perinatal period may involve in metabolizing hepatic beta-carotene, directing the retinal to the retinal reductase and leading further to the subsequent esterification of the converted retinol.

Alcohol Oxidoreductases↗
PubMed1995

Dietary maltitol increases calcium content and breaking force of femoral bone in ovariectomized rats.

Maltitol is a disaccharide alcohol generated by hydrogenation of maltose and exhibiting resistance to intestinal disaccharidases. We demonstrated previously that maltitol stimulates transepithelial transport of calcium in the ileum, accompanied by an elevation of intestinal calcium absorption as well as calcium retention in the body. In this study, we examined whether the maltitol-induced increase in intestinal calcium absorption leads to an alteration of the physical properties of bones in rats subjected to ovariectomy. We used this study as a simulation model for postmenopausal females who are at risk for osteoporosis. Following the intake of a low-calcium diet for 28 d ovariectomized rats were fed diets containing either 10% maltose (control) or 10% maltitol, together with increased amounts of calcium (0.3% in Experiment 1 and 1.2% in Experiment 2) for 21 d. Balance studies performed during the final 5-d (Experiment 1) or 2-d (Experiment 2) period of the experiments showed that maltitol increased intestinal calcium absorption and retention. The breaking force of femoral bones was significantly elevated (by 5-7%) in animals fed the maltitol diet compared with that in rats fed the maltose diet. The calcium content in the femoral bones as well as the mineral bone density of the tibial metaphysis was also elevated in rats fed the maltitol diet. These results indicate that maltitol stimulates the intestinal absorption of dietary calcium leading to an increase in calcium content in the bone, and coinciding with the elevation of the breaking strength of the bone in ovariectomized rats.

Analysis of Variance↗
PubMed1995

Unsaturated fatty acids regulate gene expression of cellular retinol-binding protein, type II in rat jejunum.

We have shown that cellular retinol-binding protein, type II (CRBP II) mRNA and its protein levels are elevated in the jejunum of rats fed a diet rich in long-chain triacylglycerols. In the present study, we explored which types of fatty acids modulate CRBP II gene expression. Rats previously fed a low fat, high starch diet were force-fed a basal fat-free diet or the diet supplemented with 0.21 mol/L of various fatty acids (i.e., caprylic, palmitic, stearic, oleic, linoleic and alpha-linolenic acids). Force-feeding a diet containing linoleic acid produced an elevation of CRBP II mRNA levels in rats in both a dose-dependent (0.053-0.21 mol/L) and time-dependent (up to 6 h) manner. Among fatty acids tested, all unsaturated fatty acids (oleic, linoleic and alpha-linolenic acids) were able to enhance CRBP II mRNA levels by 54-63% within 6 h, whereas a medium-chain fatty acid (caprylic acid) and a saturated fatty acid (stearic acid) elicited little effect on the CRBP II mRNA levels; palmitic acid produced only a small elevation (16%) of the CRBP II mRNA level. Transcripts of both retinoid X receptor alpha and peroxisome proliferator-activated receptor (PPAR), which are thought to interact as a heterodimer with the cis-element located in the CRBP II promoter and to be activated by 9-cis retinoic acid and long-chain fatty acids, respectively, were constitutively expressed in the rat jejunum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

New approach to assess quality of life in neonatal surgical cases: medical providers' subjective assessment of disease- and condition-related factors, using the linear analogue scale.

A new questionnaire survey of pediatric surgeons and nurses, using the linear analogue scale, was used to determine subjective assessments of patients' quality of life (QOL) with regard to neonatal surgical diseases and conditions, including those involving anal and urinary functions. The results were analyzed according to the medical providers' years of professional experience. For six neonatal surgical diseases, QOL was assessed more favorably by less experienced surgeons and nurses. The result was similar for adulthood diseases. The development of medical technology can be attributed to this trend; however, QOL for patients with diaphragmatic hernia was assessed less favorably by less experienced surgeons (as 66.1%) than by more experienced surgeons (as 81.6%). Current technology has enabled the survival of neonatal surgical patients who are born prematurely and/or who have serious diseases or anomalies. Consequently this leads to poorer assessment of the surviving patients' QOL. QOL for patients with imperforate anus and spina bifida remained less favorably assessed. That of patients with conditions related to anal and urinary dysfunctions also scaled in the same manner. Anal dysfunction was less favorably assessed by less experienced surgeons (as 40.0%) than by more experienced surgeons (as 49.4%). In part, this discrepancy could be attributed to (1) better adjustment by the patients to their condition over time, and (2) greater focus on QOL issues in recent years. With regard to anal function, low QOL assessment correlated strongly with imperforate anus, Hirshsprung's disease, and spina bifida (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗