Biomedical subjects

Eiji Takeda

Publications and source records attributed to Eiji Takeda.

25 records · Page 2Linked to original sources

PubMed2004

[The optimum amount of vitamin D for osteoporosis: in case of activated vitamin D treatment].

Since the resistance factors for the effect of vitamin D increases by aging, ingestion of various nutrition factors, such as calcium, and vitamin D is important for prevention and medical treatment of osteoporosis. 1 alpha 25-dihydroxyvitamin D(3) known as active form of vitamin D can stimulate calcium absorption from intestine and also it is used for the medical treatment of osteoporosis. The vitamin D action for the regulation of bone and mineral metabolism changes with the sufficiency states or the amounts of ingestion of vitamin D. Therefore, the action as a medicine is not simple. This article reviews the effect and its optimum ingestion amount of activated vitamin D in osteoporosis medical treatment.

Adult↗

PubMed2003

Increase in IP3 and intracellular Ca2+ induced by phosphate depletion in LLC-PK 1 cells.

The mechanisms by which Pi depletion rapidly regulates gene expression and cellular function have not been clarified. Here, we found a rapid increase in intracellular ionized calcium [Ca(2+)](i) by phosphate depletion in LLC-PK(1) cells using confocal microscopy with the green-fluorescence protein based calcium indicator "yellow cameleon 2.1." The increase of [Ca(2+)](i) was observed in the presence or absence of extracellular Ca(2+). At the same time, an approximately twofold increase in intracellular inositol 1,4,5-triphosphate (IP(3)) occurred in response to the acute Pi depletion in the medium. Furthermore, 2-aminoethoxydiphenyl borate completely blocked the [Ca(2+)](i) increase induced by Pi depletion. These results suggest that Pi depletion causes IP(3)-mediated release of Ca(2+) from intracellular Ca(2+) pools and rapidly increases [Ca(2+)](i) in LLC-PK(1) cells.

Animals↗

PubMed2003

Higher concentrations of interferon-gamma enhances uptake and transport of dietary antigens by human intestinal cells: a study using cultured Caco-2 cells.

Besides functioning as a mucosal barrier and transporting nutrients, intestinal epithelial cells (IECs) also serve as antigen-presenting cells (APCs). Modification of protein antigens by proteolysis is one of the principal steps in antigen presentation to Th cells. We used a Caco-2 intestinal epithelial cell line to investigate the transepithelial transport of the dietary antigen, ovalbumin (OVA). We also examined the effects of the proinflammatory cytokine interferon-gamma (IFN-gamma) on the antigen transport process in Caco-2 cell layers. Caco-2 cell layers transferred both intact and degraded OVA from the mucosal to the serosal side. IFN-gamma stimulated OVA transport and most of the transported OVA in such cells were degraded. We also examined OVA uptake by Caco-2 cells using immunohistochemical means. Caco-2 cells incorporated OVA in a time-dependent manner and IFN-gamma significantly enhanced antigen internalization. Flow cytometry also demonstrated that IFN-gamma elevated the internalization of FITC-OVA. We also determined the effects of low and high concentrations of IFN-gamma on mucosal permeability and internalization of FITC-OVA. Although both 10 and 50 ng/mL IFN-gamma stimulated mucosal permeability to the same extent, more FITC-OVA was internalized by Caco-2 cells incubated with 50 than with 10 ng/mL IFN-gamma. These results suggest that the effects of IFN-gamma on mucosal permeability and the internalization of antigens by intestinal epithelial cells are brought about by different mechanisms. Therefore, higher concentrations of IFN-gamma stimulate the uptake, processing, and transport of dietary antigens by IECs.

Antigen Presentation↗

PubMed2003

Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells.

The vitamin D(3) receptor, which is the nuclear receptor for 1alpha,25-dihydroxyvitamin D(3) (VD(3)), forms a heterodimer with the retinoid X receptor (RXR), which is the nuclear receptor for 9-cis-retinoic acid (9-cis-RA). The heterodimer binds to a specific response element consisting of two directly repeated pairs of motifs, AGGTGA, spaced by three nucleotides [direct repeat (DR) 3] and modulates the expression of VD(3)-responsive genes. Telomerase activity, which is seen in most immortal cells and germ cells, is a complex of enzymes that maintain the length of telomeres. One of the major components of human telomerase, human telomerase reverse transcriptase (hTERT), is the catalytic subunit, and the expression of hTERT might correlate most strongly with telomerase activity. We found that the sequence of 5'-AGTTCATGGAGTTCA-3' (DR3') is similar to that of DR3 in the promoter region of hTERT. Our results showed that the combination of VD(3) and 9-cis-RA inhibited telomerase activity through direct interaction of the heterodimer of vitamin D(3) receptor and RXR with the DR3' sequence in the hTERT promoter as well as the combination of VD(3) and selective RXR ligand did. Also, in vivo data showed that the growth of xenografts in nude mice was inhibited by VD(3) and 9-cis-RA. The results of the present study provide evidence on the molecular mechanism of the inhibition of cell growth by these agents, and they could be novel therapeutic agents for prostate cancer.

Alitretinoin↗

PubMed2002

Hydrogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells: potential role in cell survival following oxidative insults.

Reactive oxygen species, generated by reduction-oxidation (redox) reactions, have been recognized as one of the major mediators of ischemia and reperfusion injury in the brain. Reactive oxygen species-induced cerebral events are attributable, in part, to the change in intracellular signaling molecules including mitogen-activated protein (MAP) kinases. Big MAP kinase 1 (BMK1), also known as ERK5, is a newly identified member of the MAP kinase family and has been reported to be sensitive to oxidative stress. In the present study, we examined the effect of H(2)O(2) on BMK1 activity in PC12 cells, and we investigated the pathophysiological implication of BMK1. Findings showed that BMK1 was rapidly and significantly activated by H(2)O(2) in a concentration-dependent manner in PC12 cells. BMK1 activation by H(2)O(2) was inhibited by both PD98059 and U0126, which were reported to inhibit MEK5 as well as MEK1/2. c-Src was suggested to be involved in BMK1 activation from the experiments with herbimycin A and PP2, specific inhibitors of Src family kinases. Transfection of kinase-inactive Src also inhibited H(2)O(2)-induced BMK1 activation. In addition, H(2)O(2) treatment of cells induced an enhancement of DNA binding activity of MEF2C, a downstream transcription factor of BMK1 in PC12 cells. Finally, pretreatment of cells with PD98059 and U0126 resulted in an increase in cell death including apoptosis by H(2)O(2) in ERK1/2 down-regulated cells as well as in intact PC12 cells. These findings suggest that c-Src mediated BMK1 activation by H(2)O(2) may counteract ischemic cellular damage probably through the activation of MEF2C transcription factor.

Animals↗

PubMed2002

Phosphorus supply per capita from food in Japan between 1960 and 1995.

The awareness of phosphorus intake is important because hyperphosphatemia and hypophosphatemia both impair bone metabolism. Phosphorus consumption from food was obtained from values in the Food Balance Sheet (PBS) of Japan from 1960 to 1995. The amounts of phosphorus calculated from the FBS increased gradually from 1,243 mg/d in 1960 to 1,332 mg/d in 1975 and to 1,421 mg/d in 1995. This is explained by the increased consumption of cow's milk and milk products, meat, and chicken eggs. The main foods supplying phosphorus in 1995 were cereals, milk and milk products, fishes and shellfishes, and vegetables; their contributions were 24.4, 15.8, 14.2, and 10.9%, respectively. The phosphorus-to-calcium ratio calculated from the FBS was 3.51 in 1960, which decreased to 2.89 in 1975 and 2.44 in 1995. Therefore total phosphorus consumption in 1995 was presumably more than 1,500 mg/d when imported food containing phosphorus and the consumption of phosphorus-containing food additives in Japan are also considered. These findings suggest that the phosphorus consumption estimated from the FBS is increasing and that more attention should be paid to the maintenance of healthy bones in Japan, where the average amount of calcium intake is less than 600 mg/d.

Bone and Bones↗

PubMedDate not supplied

Inorganic phosphate homeostasis and the role of dietary phosphorus.

Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by Pi, parathyroid hormone and by 1,25-dihydroxyvitamin D. Recent studies of inherited and acquired hypophosphatemia [X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced rickets/osteomalacia (TIO)], which exhibit similar biochemical and clinical features, have led to the identification of novel genes, PHEX and FGF23, that play a role in the regulation of Pi homeostasis. The PHEX gene, which is mutated in XLH, encodes an endopeptidase, predominantly expressed in bone and teeth, but not in kidney. FGF-23 may be a substrate of this endopeptidase and may therefore accumulate in patients with XLH. In the case of ADHR mutations in the furin cleavage site, which prevent the processing of FGF-23 into fragments, lead to the accumulation of a "stable" circulating form of the peptide which also inhibits renal Pi reabsorption. In the case of TIO, ectopic overproduction of FGF-23 overwhelms its processing and degradation by PHEX, leading to the accumulation of FGF-23 in the circulation and inhibition of renal Pi reabsorption. Mice homozygous for severely hypomorphic alleles of the Klotho gene exhibit a syndrome resembling human aging, including atherosclerosis, osteoporosis, emphysema, and infertility. The KLOTHO locus is associated with human survival, defined as postnatal life expectancy, and longevity, defined as life expectancy after 75. In considering the relationship of klotho expression to the dietary Pi level, the klotho protein seemed to be negatively controlled by dietary Pi.

Animals↗