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7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway
| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Yuta Sato Noriko Ishihara Daiji Nagayama Atsuhito Saiki Ichiro Tatsuno |
| Abstract | 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. |
| Related Links | http://www.sciencedirect.com/science/article/pii/S2214426916301161 |
| ISSN | 22144269 |
| DOI | 10.1016/j.ymgmr.2017.01.006 |
| Journal | Molecular Genetics and Metabolism Reports |
| Issue Number | C |
| Volume Number | 10 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2017-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Medicine (General) Biology (General) 7-ketocholesterol Mc3t3-e1 Cells Reactive Oxygen Species (ros) N-acetylcysteine (nac) Apoptosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Molecular Biology Endocrinology |