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  • 标题:7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway
  • 本地全文:下载
  • 作者:Yuta Sato ; Noriko Ishihara ; Daiji Nagayama
  • 期刊名称:Molecular Genetics and Metabolism Reports
  • 印刷版ISSN:2214-4269
  • 出版年度:2017
  • 卷号:10
  • 页码:56-60
  • DOI:10.1016/j.ymgmr.2017.01.006
  • 出版社:Elsevier B.V.
  • 摘要:Highlights

    We examined the effects of 7-ketocholesterol (7KCHO) on MC3T3-E1 cells.

    7KCHO increased reactive oxygen species (ROS) and apoptosis.

    7KCHO enhanced CHOP and GRP78 expression.

    N -acetylcysteine suppressed 7KCHO-induced ROS, apoptosis and CHOP expression.

    Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway. Furthermore, these effects of 7KCHO were abolished by pre-incubation of the cells with N -acetylcysteine (NAC), an ROS inhibitor. Also, 7KCHO enhanced the mRNA expression of two endoplasmic reticulum (ER) stress markers; CHOP and GRP78, in MC3T3-E1 cells. Pre-incubation of the cells with NAC suppressed the 7KCHO-induced upregulation of CHOP, but not GRP78. In conclusion, we demonstrated that 7KCHO induced apoptosis of MC3T3-E1 cells associated with ROS generation, ER stress, and caspase-3/7 activity, and the effects of 7KCHO were abolished by the ROS inhibitor NAC. These findings may provide new insight into the relationship between oxysterol and pathophysiology of osteoporosis seen in T2DM.

  • 关键词:7-ketocholesterol; MC3T3-E1 cells; Reactive oxygen species (ROS); N-acetylcysteine (NAC); Apoptosis
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