Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
最新号
選択された号の論文の6件中1~6を表示しています
Full Papers
  • Sayuri TAKAHASHI, Mako KUROGI, Osamu SAITOH
    原稿種別: research-article
    2021 年 42 巻 2 号 p. 43-51
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    The perception of tastes is sensed by the receptors that stimulate sensory cells. We previously reported that TRPA1 and TRPV1 channels expressed in the oral cavity of mammals, are activated by the auto-oxidized product of epigallocatechin gallate (oxiEGCG), a major astringent catechin in green tea. Here, we investigated and compared the sensitivity of TRPA1 and TRPV1 from various animals to astringent polyphenols. We selected three polyphenols, oxiEGCG, tannic acid and myricetin. HEK293T cells expressing TRPA1 or TRPV1 from mammal, bird, reptile, amphibian, and fish, were analyzed for their activation by the Ca2+-imaging. We found the apparent diversity in the polyphenol-sensitivity among various animals. Mammalian TRPs showed relatively higher sensitivity to polyphenols, and especially, human TRPA1 and TRPV1 could be activated by all of three polyphenols at 20 μM. Reptile TRP channels, however, were insensitive to any polyphenols examined. Moreover, the polyphenol-sensitivity of zebrafish TRPA1 and TRPV1 was quite different from that of medaka TRP channels. Since many polyphenols are present in plants and the sensing of polyphenols using TRP channels in the oral cavity might cause astringent taste, the observed diversity of the polyphenol-sensitivity of TRP channels might be involved in the divergence in the food habit of various animals.

  • Hideki YAMAMOTO, Chikako TOMIYAMA, Ko SATO, Jun KASAMATSU, Kazuki TAKA ...
    原稿種別: research-article
    2021 年 42 巻 2 号 p. 53-66
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow–derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-α-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

  • Risa TAKAHARA-YAMAUCHI, Hideshi IKEMOTO, Takayuki OKUMO, Fatma Zahra S ...
    2021 年 42 巻 2 号 p. 67-76
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    In this study, we employed a rodent model for persistent allodynia and hyperalgesia to determine whether voluntary exercise could exert analgesic effects on these pain symptoms. Rats were subcutaneously injected with formalin into the plantar surface of the right hind paw to induce mechanical allodynia and hyperalgesia. We assessed the analgesic effects of a voluntary wheel running (VWR) using the von Frey test and investigated microglial proliferation in the dorsal horn of the spinal cord. We also determined the effect of formalin and VWR on the protein expression levels of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and K+-Cl cotransporter 2 (KCC2), which play a key role in inducing allodynia and hyperalgesia. Rats with access to the running wheels showed beneficial effects on persistent formalin-induced mechanical allodynia and hyperalgesia. The effects of VWR were elicited through the suppression of formalin-induced microglial proliferation, TrkB up-regulation, and KCC2 down-regulation in the spinal cord. BDNF, however, might not contribute to the beneficial effects of VWR. Our results show an analgesic effect of voluntary physical exercise in a rodent model with persistent pain, possibly through the regulation of microglial proliferation and TrkB and KCC2 expression in the spinal cord.

  • Woo KIM, Haruhiko TOKUDA, Kumiko TANABE, Shinobu YAMAGUCHI, Tomoyuki H ...
    原稿種別: research-article
    2021 年 42 巻 2 号 p. 77-84
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    Acetaminophen is one of the most widely used analgesic and antipyretic medicines, whose long-period use has reportedly been associated with an increased risk of bone fracture. However, the mechanism underlying this undesired effect remains to be investigated. The homeostatic control of bone tissue depends on the interaction between osteoblasts and osteoclasts. Osteoprotegerin produced by osteoblasts is known to play an essential role in suppressing osteoclast induction. We have previously reported that prostaglandin (PG) E2 and PGF induce osteoprotegerin synthesis through p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of acetaminophen on the osteoprotegerin synthesis induced by PGE2 and PGF in MC3T3-E1 cells. Acetaminophen significantly suppressed the osteoprotegerin release stimulated by PGE2 and PGF. The PGE2-induced expression of osteoprotegerin mRNA was also reduced by acetaminophen. Acetaminophen markedly downregulated the phosphorylation of SAPK/JNK stimulated by PGE2 and PGF, but not those of p38 MAPK or p44/p42 MAPK. SP600125, an inhibitor of SAPK/JNK, suppressed the levels of PGE2- and PGF-upregulated osteoprotegerin mRNA expression. Taken together, these results strongly suggest that acetaminophen reduces the PGE2- and PGF-stimulated synthesis of osteoprotegerin in osteoblasts, and that the suppressive effect is exerted via attenuation of SAPK/JNK. These findings provide a molecular basis for the possible effect of acetaminophen on bone tissue metabolism.

Communication
  • Masaya SHIMADA, Mayu HIBI, Tomoyuki NAKAGAWA, Takashi HAYAKAWA, Cather ...
    原稿種別: research-article
    2021 年 42 巻 2 号 p. 85-88
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in the biosynthesis of monounsaturated fatty acids, and the expression of the Scd1 gene is induced by the intake of the lipogenic sugar fructose. We examined the effects of a high-fructose diet on hepatic acetylation of histones H3 and H4 and the binding of carbohydrate response element-binding protein (ChREBP) on the Scd1 gene promoter in rats. Rats were fed a control diet or a high-fructose diet for 10 days. The intake of a high-fructose diet significantly increased histone H3 and H4 acetylation and ChREBP binding to the Scd1 gene promoter as well as the amount of triglyceride and the expression of the Scd1 gene. These results suggest that short-term intake of high fructose upregulates expression of Scd1 by enhancing acetylation of histones H3 and H4 and binding of ChREBP at the Scd1 promoter.

  • Akane NARUOKA, Sumiko OHNAMI, Takeshi NAGASHIMA, Masakuni SERIZAWA, Ke ...
    原稿種別: research-article
    2021 年 42 巻 2 号 p. 89-94
    発行日: 2021/04/10
    公開日: 2021/04/10
    ジャーナル フリー

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor syndrome. This hereditary cancer is caused by germline variants in MEN1. Two patients with MEN1 were identified via whole exome sequencing and gene expression profile analysis, conducted for 5,063 patients with various types of cancers. We obtained multiple tumors from each patient; tumors derived from these two MEN1 patients had a loss of the normal MEN1 allele and frequently chromosomal copy number changes. Thus, we investigated whether structural variants were present in the MEN1 patient genomes. Whole-genome sequencing revealed no catastrophic rearrangements, and the tumor samples had very low somatic variants. The two patients had germline variants in MEN1 and some chromosomal copy number changes including on chromosome 11. The only pathogenic variant detected was the MEN1 germline variant, and chromosomal rearrangements led to tumorigenesis in somatic cells. Furthermore, the MEN1 tumor samples displayed a specific signature characterized by T:A>C:G transition. Studies of multiple tumors obtained from single patients are rare in hereditary cancer syndromes, and our results provide insights that the second hit of the tumor suppressor gene MEN1 may be caused by a gross genome rearrangement, not a small insertion and deletion, nor a change in epigenetic regulation.

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