著者

Koji Yamashita Tadaatsu Imaizumi Masaharu Hatakeyama Wakako Tamo Daisuke Kimura Mika Kumagai Hidemi Yoshida Kei Satoh

出版者

Tohoku University Medical Press

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.200, no.4, pp.187-194, 2003 (Released:2004-09-08)

参考文献数

35

被引用文献数

15 16

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CX3CL1-/fractalkine is a chemokine with a unique CX3C motif. Hypoxia mediates the expression of various genes, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2, and plasminogen-activator inhibitor-1, in vascular endothelial cells. We studied the eect of hypoxia on the expression of fractalkine induced by interferon-γ (IFN-γ) in endothelial cells. Human umbilical vein endothelial cells were cultured, and the stimulation of the cells with IFN-γ was found to induce the expression of fractalkine. Hypoxia inhibited the expression of fractalkine mRNA and protein by IFN-γ, and this eect was observed with concomitant increase in VEGF expression. Desferrioxamine, an iron chelator that mimics hypoxia in vitro, also inhibited the fractalkine production induced by IFN-γ. Hypoxia did not aect the degradation of fractalkine mRNA. The inhibition of fractalkine expression by hypoxia was reversed on returning the cultures to reoxygenation condition. Inhibition of IFN-induced fractalkine expression by hypoxia was not aected by the presence of a radical scavenger, N-acetyl-L-cysteine, and the involvement of reactive oxygen species may be excluded. Inhibition of fractalkine expression by hypoxia may be involved in the pathophysiology of ischemic diseases.

著者

Syota SEINO Takeru KIMOTO Hidemi YOSHIDA Kunikazu TANJI Tomoh MATSUMIYA Ryo HAYAKARI Kazuhiko SEYA Shogo KAWAGUCHI Kazushi TSURUGA Hiroshi TANAKA Tadaatsu IMAIZUMI

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.39, no.3, pp.105-115, 2018-06-01 (Released:2018-06-12)

参考文献数

41

被引用文献数

10 15

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Accumulation and oligomerization of amyloid-beta (Aβ) peptides have been known to be a potent cause of neurodegenerative diseases such as Alzheimer’s disease (AD). To expand the possibilities of preventing AD, we investigated the effects of resveratrol dimers, gnetin C and ε-viniferin, on Aβ 1–42 (Aβ42) production and the reduced cell viability observed after Aβ42 treatment (monomers, 10 μM) in cultured SH-SY5Y human neuroblastoma cells. Among them, addition of gnetin C (20 μM) into the media reduced Aβ42 production most efficiently. Gnetin C suppressed the expression of β-site amyloid precursor protein-cleaving enzyme-1 (BACE1, β-secretase). Furthermore, gnetin C ameliorated the Aβ42-reduced cell viability most significantly. Concomitantly, gnetin C reduced intracellular Aβ oligomers (ca. 15 and 130 kDa) and elevated both levels of intracellular and extracellular Aβ monomers. Under the treatment with or without Aβ42, gnetin C upregulated the expression of matrix metalloproteinase-14 (MMP-14) which is assumed to be an Aβ-decomposing enzyme. Gnetin C may thereby prevent Aβ toxicity by suppressing BACE1 and enhancing MMP-14, together with reducing both internalization and oligomerization of exogenous Aβ monomers. The use of gnetin C may lead to the prevention of Aβ-mediated diseases, particularly AD.