期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2019, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2019/4101738
关键词
-
类别
资金
- Natural Science Foundation of China [81500817, 81870777, 81802230]
- Zhejiang Provincial Natural Science Foundation of China [LY15H140008]
- Health Science and Technology Project of Zhejiang Province [2016KYB184]
- Zhejiang Provincial Science and Technology Project for Public Welfare [2017C33081, GF19H140006]
- Zhejiang Traditional Chinese Medicine Research Fund Project [2019ZB077]
- Key Laboratory of Orthopedics of Zhejiang Province [ZJGK1807Y]
- Wenzhou Municipal Science and Technology Project for Public Welfare [Y20150069, Y20170026, Y20180160]
- Wenzhou Science and Technology Bureau [Y20160051, Y20140704]
- Zhejiang Provincial College Students' Science and Technology Innovation Project and Fresh Talent Program [2017R413067, 2017R413082]
Oxidative stress (OS) induces osteoblast apoptosis, which plays a crucial role in the initiation and progression of osteoporosis. Although OS is closely associated with mitochondrial dysfunction, detailed mitochondrial mechanisms underlying OS-induced osteoblast apoptosis have not been thoroughly elucidated to date. In the present study, we found that mitochondrial abnormalities largely contributed to OS-induced osteoblast apoptosis, as evidenced by enhanced production of mitochondrial reactive oxygen species; considerable reduction in mitochondrial respiratory chain complex activity, mitochondrial membrane potential, and adenosine triphosphate production; abnormality in mitochondrial morphology; and alteration of mitochondrial dynamics. These mitochondrial abnormalities were primarily mediated by an imbalance in mitochondrial fusion and fission through a protein kinase B- (AKT-) glycogen synthase kinase 3 beta- (GSK3 beta-) optic atrophy 1- (OPA1-) dependent mechanism. Hydroxytyrosol (3,4-dihydroxyphenylethanol (HT)), an important compound in virgin olive oil, significantly prevented OS-induced osteoblast apoptosis. Specifically, HT inhibited OS-induced mitochondrial dysfunction by decreasing OPA1 cleavage and by increasing AKT and GSK3 beta phosphorylation. Together, our results indicate that the AKT-GSK3 beta signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT could be an effective nutrient for preventing osteoporosis development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据