ダウンロード数 : ?
ファイル
言語
英語
著者
田中 賢一郎
横本 真希
山口 徹
内容記述(抄録等)
Background: Elevated plasma homocysteine (Hcy) level is associated with the risk of osteoporotic fracture. While Hcy increases oxidative stress, AMP-activated protein kinase (AMPK) activation ameliorates it. This study aimed to investigate whether Hcy induces apoptosis of osteocytic MLO-Y4 cells through regulating expressions of oxidant and anti-oxidant enzymes and determine the effects of AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and metformin on the Hcy-induced apoptosis of the cells.
Results: DNA fragment ELISA and TUNEL staining assays showed that Hcy treatments (0.1-5.0 mM) induced apoptosis of MLO-Y4 cells in a dose-dependent manner. The detrimental effect of Hcy was partly but significantly reversed by an antioxidant (N-acetylcysteine) and NADPH oxidase (Nox) inhibitors (apocynin and diphenyleneiodonium). In addition, treatment with AICAR (0.05-0.1 mM) and metformin (10-100 μM) ameliorated Hcy-induced apoptosis of the cells. The favorable effect of metformin on Hcy-induced apoptosis was completely canceled by an AMPK inhibitor Ara-A. Hcy increased the expression levels of Nox1 and Nox2, while it had no effects on the expressions of Nox4 or the anti-oxidant enzymes, superoxide dismutase 1 and 2. Hcy-induced increases in the expressions of Nox1 and Nox2 decreased significantly by treatments with AICAR.
Conclusion: These findings suggest that Hcy induces apoptosis of osteocytes by increasing the expressions of Nox1 and Nox2, and AMPK activation by AICAR and metformin effectively prevents the detrimental reactions. Thus, AMPK activation may be a potent therapeutic candidate for preventing Hcy-induced osteocyte apoptosis and the resulting bone fragility.
主題
Homocysteine
Osteocyte
AMP-activated protein kinase
Oxidative stress
NADPH oxidase
掲載誌名
Bone
77
開始ページ
135
終了ページ
141
ISSN
87563282
発行日
2015-08
DOI
DOI公開日
2017-04-10
PubMed ID
出版者
Elsevier
資料タイプ
学術雑誌論文
ファイル形式
PDF
権利関係
© 2015 Elsevier Inc. All rights reserved.
著者版/出版社版
著者版
業績ID
e28544
e28617
部局
医学部
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