Yohei Abe

Characterization of Novel Staphylococcal Enterotoxin-Like Toxin Type P

ABSTRACT We investigated the biological properties of a novel staphylococcal enterotoxin (SE)-like toxin type P (SElP). SElP induced a substantial proliferative response and the production of cytokines interleukin-2, gamma interferon, tumor necrosis factor alpha, and interleukin-4 from human T cells when administered at a concentration of 0.4 pM (0.01 ng/ml) or more. The expression of major histocompatibility complex class II molecules on accessory cells was required for T-cell stimulation by SElP. SElP selectively stimulated a vast number of human T cells bearing receptors Vβ 5.1, 6, 8, 16, 18, and 21.3. These results indicated that SElP acts as a superantigen. SElP proved to be emetic in the house musk shrew emetic assay, although at a relatively high dose (50 to 150 μg/animal). A quantitative assay of SElP production with 30 Staphylococcus aureus strains harboring selp showed that 60% of these strains produced significant amounts of SElP in vitro. All 10 strains carrying seb and selp produced SEB but not SElP, suggesting the inactivation of the selp locus in S. aureus strains with a particular se gene constitution.

JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis

Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the β1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound PPARγ. This complex confers β-adrenergic-induced rapid JMJD1A recruitment to target sites and facilitates long-range chromatin interactions and target gene activation. This rapid gene induction is dependent on S265 phosphorylation but not on demethylation activity. Our results show that JMJD1A has two important roles in regulating hormone-stimulated chromatin dynamics that modulate thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and functions as a cAMP-responsive scaffold that facilitates long-range chromatin interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation.

The role of hypertriglyceridemia in the development of atherosclerosis and endothelial dysfunction.

A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit) is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated postprandially compared with healthy Japanese white (JW) rabbits. In physiological experiments, the ring preparation of the thoracic aorta was suspended in an organ bath filled with modified Krebs-Henseleit solution, and the developed tension was recorded. Endothelial function was evaluated by acetylcholine-induced vasorelaxation in each preparation with intact endothelium. The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits. Histological examination was carried out in adipose tissue, liver and aorta. They were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4 μm) and stained using hematoxylin-eosin solution. In the adipose tissue, the visceral fat accumulated, and the size of adipose cells was enlarged in PHT rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta, increased intimal thickness was observed, suggesting the progression of atherosclerosis in the PHT rabbit. This study suggests the important role of postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the effects of hypertriglyceridemia on health and diseases could be evaluated precisely.

The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis

Background: Polycomb repressive complex PRC1 is an epigenetic regulator of cellular differentiation. However, its function during adipogenesis is unknown. Results: FBXL10/KDM2B recruited noncanonical PRC1 complex in F-box and LRR motifs dependent on cell cycle-related genes and Pparg genes and repressed 3T3-L1 adipogenesis. Conclusion: Noncanonical PRC1 complex containing FBXL10/KDM2B regulates adipogenesis. Significance: Our findings revealed a novel epigenetic mechanism of adipogenesis. Polycomb repressive complex 1 (PRC1) plays an essential role in the epigenetic repression of gene expression during development and cellular differentiation via multiple effector mechanisms, including ubiquitination of H2A and chromatin compaction. However, whether it regulates the stepwise progression of adipogenesis is unknown. Here, we show that FBXL10/KDM2B is an anti-adipogenic factor that is up-regulated during the early phase of 3T3-L1 preadipocyte differentiation and in adipose tissue in a diet-induced model of obesity. Interestingly, inhibition of adipogenesis does not require the JmjC demethylase domain of FBXL10, but it does require the F-box and leucine-rich repeat domains, which we show recruit a noncanonical polycomb repressive complex 1 (PRC1) containing RING1B, SKP1, PCGF1, and BCOR. Knockdown of either RING1B or SKP1 prevented FBXL10-mediated repression of 3T3-L1 preadipocyte differentiation indicating that PRC1 formation mediates the inhibitory effect of FBXL10 on adipogenesis. Using ChIP-seq, we show that FBXL10 recruits RING1B to key specific genomic loci surrounding the key cell cycle and the adipogenic genes Cdk1, Uhrf1, Pparg1, and Pparg2 to repress adipogenesis. These results suggest that FBXL10 represses adipogenesis by targeting a noncanonical PRC1 complex to repress key genes (e.g. Pparg) that control conversion of pluripotent cells into the adipogenic lineage.

High Affinity of Interaction between Superantigen and T Cell Receptor Vβ Molecules Induces a High Level and Prolonged Expansion of Superantigen-reactive CD4+ T Cells

In mice implanted with an osmotic pump filled with the superantigen (SAG) staphylococcal enterotoxin A (SEA), the Vβ3+CD4+ T cells exhibited a high level of expansion whereas the Vβ11+CD4+ T cells exhibited a mild level of expansion. In contrast, in mice implanted with an osmotic pump filled with SE-like type P (SElP, 78.1% homologous with SEA), the Vβ11+CD4+ T cells exhibited a high level of expansion while the Vβ3+CD4+ T cells exhibited a low level of expansion, suggesting that the level of the SAG-induced response is determined by the affinities between the TCR Vβ molecules and SAG. Analyses using several hybrids of SEA and SElP showed that residue 206 of SEA determines the response levels of Vβ3+CD4+ and Vβ11+CD4+ T cells both in vitro and in vivo. Analyses using the above-mentioned hybrids showed that the binding affinities between SEA and the Vβ3/Vβ11 β chains and between SEA-MHC class II-molecule complex and Vβ3+/Vβ11+ CD4+ T cells determines the response levels of the SAG-reactive T cells both in vitro and in vivo.

Objective evaluation of whiteness of cooked rice and rice cakes using a portable spectrophotometer

The whiteness of cooked rice and rice cakes was evaluated using a portable spectrophotometer with a whiteness index (WI). Also, by using boiled rice for measurement of Mido values by Mido Meter, it was possible to infer the whiteness of cooked rice without rice cooking. In the analysis of varietal differences of cooked rice, ‘Tsuyahime’, ‘Koshihikari’ and ‘Koshinokaori’ showed high whiteness, while ‘Satonoyuki’ had inferior whiteness. The whiteness of rice cakes made from ‘Koyukimochi’ and ‘Dewanomochi’ was higher than the whiteness of those made from ‘Himenomochi’ and ‘Koganemochi’. While there was a significant correlation (r = 0.84) between WI values and whiteness scores of cooked rice by the sensory test, no correlation was detected between the whiteness scores and Mido values, indicating that the values obtained by a spectrophotometer differ from those obtained by a Mido Meter. Thus, a spectrophotometer may be a novel device for measurement of rice eating quality.

Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function

Non-coding genetic variation is a major driver of phenotypic diversity and allows the investigation of mechanisms that control gene expression. Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. We observed substantial differences associated with distinct molecular pathways. Evaluating genetic variation provided evidence for roles of ∼100 TFs in shaping lineage-determining factor binding. Unexpectedly, a substantial fraction of strain-specific factor binding could not be explained by local mutations. Integration of genomic features with chromatin interaction data provided evidence for hundreds of connected cis-regulatory domains associated with differences in transcription factor binding and gene expression. This system and the >250 datasets establish a substantial new resource for investigation of how genetic variation affects cellular phenotypes.

Effects of Scirpusin B, a polyphenol in passion fruit seeds, on the coronary circulation of the isolated perfused rat heart -

Piceatannol, a polyphenol which is contained in passion fruits seed, is a derivative of resveratrol and is known to have antioxidant, anti-inflammatory and vasorelaxing activities. Passion fruits seed also contains a dimer of Piceatannol, Scirpusin B. The aim of this study was to investigate the effect of Scirpusin B on the coronary circulation of the isolated rat heart. Methods: Hearts were isolated from male Fischer 344 rats (5 - 6 months old), and perfused with modified Krebs-Henseleit solution aerated with 95% O2 and 5% CO2 (37 °C) at constant pressure (75 cmH2O) by Langendorffs method. Piceatannol or Scirpusin B (10, 30 and 100 μM)was injected as a bolus into the aortic cannula and coronary flow (CF) was continuously measured by the electromagnetic flow meter. In some experiments, rat hearts were pretreated with L-NAME (an inhibitor of nitric oxide synthase) or Diclofenac (an inhibitor of cyclooxygenase) to reveal the possible involvement of nitric oxide (NO) and vasodilating prostanoids in the effect of Scirpusin B. Results:Scirpusin B increased CF up to 108.2 % of the initial value, while Piceatannol did not increase CF. In addition;Scirpusin B increased CF concentrationdependently. Pretreatment with L-NAME or Diclofenac significantly attenuated the Scirpusin B-induced coronary vasodilatation. Scirpusin B did not change the heart rate either left ventricular pressure. Conclusion:This study shows that Scirpusin B could increase CF via production of NO and vasodilating prostanoids

Effects of 2-Octynyladenosine (YT-146) on Mitochondrial Function in Ischemic/Reperfused Rat Hearts

This study investigated the effects of an adenosine receptor agonist, 2-octynyladenosine (YT-146), on mitochondrial function in ischemic and ischemic/reperfused hearts. Isolated rat hearts were perfused in the Langendorff manner with a constant flow rate, and exposed to 30 min of ischemia followed by 60 min of reperfusion. Preischemic treatment with YT-146 significantly improved postischemic recovery of left ventricular developed pressure. The high-energy phosphate content in reperfused hearts treated with YT-146 was also more greatly restored than in untreated hearts. YT-146 treatment attenuated the Na(+) content of a mitochondria-enriched fraction, but not the myocardial Na(+) content, at the end of ischemia. These results suggest that preischemic YT-146 treatment preserves the energy-producing ability of mitochondria during ischemia in the Na(+)-accumulated myocardium. YT-146 also attenuated both the sodium lactate-induced decrease in mitochondrial energy-producing ability and the increase in mitochondrial Na(+) concentration in the myocardial skinned fibers. YT-146 may attenuate Na(+) influx to myocardial mitochondria in ischemic cardiac cells, resulting in both preservation of the ability of mitochondria to produce energy and enhancement of the contractile recovery in reperfused hearts. Our findings suggest that the cardioprotective effects of YT-146 against ischemia/reperfusion injury are at least partially due to the preservation of mitochondrial function in the ischemic myocardium.