FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis

Fibroblast growth factor 23 (FGF-23) and Klotho are secretory proteins that regulate mineral-ion metabolism. Fgf-23(-/-) or Klotho(-/-) knockout mice exhibit several pathophysiological processes consistent with premature aging including severe atrophy of tissues. We show that the signal transduction pathways initiated by FGF-23-Klotho prevent tissue atrophy by stimulating proliferation and preventing apoptosis caused by excessive systemic vitamin D. Because serum levels of active vitamin D are greatly increased upon genetic ablation of Fgf-23 or Klotho, we find that these molecules have a dual role in suppression of apoptotic actions of vitamin D through both negative regulation of 1alpha-hydroxylase expression and phosphoinositide-3 kinase-dependent inhibition of caspase activity. These data provide new insights into the physiological roles of FGF-23 and Klotho.     

Seasonal Dynamics of Dimethylarsenic Acid Degrading Bacteria Dominated in Lake Kibagata

Degradation processes of organoarsenic compounds significantly influence arsenic cycles in aquatic environments and would depend on the bacterial activities. The bacterial population involving dimethylarsinic acid (DMAA) degradation was investigated in Lake Kibagata from April to December in 2003. During the experimental period, the methylated arsenic was not detected, although the inorganic arsenic concentration ranged from 3.4 nM to 9.2 nM. Moreover, in the sample water of Lake Kibagata to which DMAA added, DMAA decreased while inorganic arsenic increased for 25 days. These facts suggested that the bacteria remineralized methylate arsenic species to inorganic arsenic. In fact, monitoring the use of Most Probable Number (MPN) procedure demonstrated that the DMAA-degrading bacteria exist at cell densities ranged from 41 cells/ml to 510 cells/ml. To determine the composition of DMAA-degrading bacteria, the total 110 isolates obtained as dominated bacterial species were analyzed by the restriction-fragment-length polymorphism (RFLP) analysis of 16S rDNA. As a result, total 110 isolates were classified into 12 types, of which 4 types dominated during the spring and/or fall seasons, and the rest 8 types dominated during summer season. DMAA degrading activities of the 110 isolates ranged at various degrees. Especially, the some isolates of fall season tend to show high degradation activities. The phylogenetic analysis using 16S rDNA revealed that the representative isolates formed several clusters in the gram-positive bacterial group and the proteobacteria subdivision. The diverse compositions of DMAA-degrading bacteria would seasonally change to control the rates of organoarsenic degradation in Kibagata.     

Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47(phox), p67(phox), gp91(phox) and Nox4), fibrosis markers (TGF-β(1) and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis.     

TLC screening of thraustochytrid strains for squalene production

Screenings of thraustochytrids (Labyrinthulomycetes) have been conducted for 176 strains isolated from various sites in the Asian region to investigate what type of species and strains accumulate high levels of squalene. Thin layer chromatography (TLC) screening for squalene production revealed that 38 strains were rated as “+” (high), 29 as “±” (medium), and 109 as “?” (low). Further, high performance liquid chromatography analysis strongly supported the TLC screening results. Besides the 18W-13a strain of Aurantiochytrium sp., which was previously recognized as a squalene-rich strain, several strains produced squalene at approximately 1 g L^?1 of culture volume. Squalene production was strongly related to locality, colony color, and phylogenetic clade. Most strains with “+” squalene spots were isolated from Okinawa, a subtropical region of Japan, while the strains with “±” and “?” squalene spots were isolated from wide geographical regions from tropical to subarctic. Approximately half the strains with orange colonies on GTY medium plates produced a high amount of squalene, whereas the other strains with different colors showed less or no squalene spots on TLC. All the squalene-rich strains were assigned to the Aurantiochytrium clade. Overall, our results suggest that (1) the thraustochytrids show tendentious locality in terms of squalene production, (2) a relationship exists between the metabolic synthesis of carotenoid pigments and squalene production, and (3) the Aurantiochytrium clade may have evolved to accumulate squalene.     

Changes of Linoleic,Arachidonic and Eicosapentaenoic Acids in Rat Platelet,Aorta and Plasma Lipids after Changing from a Sardine Oil Diet to a Corn Oil Diet

When rats were fed on a diet containing sardine oil (SO) for 10 days, 20:5 (eicosapentaenoic acid) was incorporated into the platelet, aorta and plasma lipids. The 20:5/20:4 (arachidonic acid) ratios of phospholipids were higher in platelets than in aortas. When the diet was changed from SO to corn oil (CO), the levels of 20:5 in the plasma lipids and platelet phospholipids decreased with an increase of 20:4. Although the 20:5 levels of phospholipids in the aortas decreased, 20:4 did not increase during feeding with the CO diet for 4 days. The 20:5/20:4 ratios of the phosphatidylcholine in platelets and aortas rapidly changed from 5.0 and 1.1 to 2.4 and 0.6, respectively. The linoleic acid level of phosphatidylcholine in platelets and aortas increased rapidly by changing from the SO diet to the CO diet, but this fatty acid was not incorporated into phosphatidylinositol of the platelets and aortas.     

Design, total synthesis, and biological evaluation of neodysiherbaine A derivative as potential probes

To enable studies to elucidate the detailed biological function of dysiherbaine and neodysiherbaine A, potent and subunit-selective agonists for ionotropic glutamate receptors, the derivative with a hydroxymethyl substituent at the C10 position has been developed. Preliminary biological evaluation of the analogue showed that a C10 hydroxymethyl substituent produced significant alterations in binding affinities for the ionotropic glutamate receptor subtypes.     

Studies on Egg White Proteins

Four components of ovomucoid were digested exhaustively and four kinds of glycopeptide corresponding to the four components were separated by gel filtration. Each glycopeptide was shown to be homogenious by paper chromatography and paper electrophoresis. Molar ratios of carbohydrate components of these glycopeptides varied to some extent but the amino acid compositions of these glycopeptides were essentially identical with each other with the exception of alanine. Aspartic acid and threonine were predominant amino acids in the all glycopeptides. It is most likely that the modes of linkages between polysaccharide and protein in individual ovomucoid I, II, III and IV are essentially the same, and that the carbohydrate moiety is linked to the protein via asparaginyl residue or the hydroxyl group of threonine, although the possibility of the linkages to glutamine and serine can not be excluded.