AKT-GSK3 β Signaling Pathway Regulates Mitochondrial Dysfunction-Associated OPA1 Cleavage Contributing to Osteoblast Apoptosis: Preventative Effects of Hydroxytyrosol

作者：Wen‐Wu Cai, Yu Chen, Linda Shi, Hao Ran Cheng, Isaac Banda, Yu Ji, Yuenv Wang, Xindong Li, Yixin Mao, D. F. Zhang, Panpan Dai, Xiaoyu Sun, Xinjie Ning, Shengbin Huang, J. F., S. F. Zhao · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2019 · DOI：10.1155/2019/4101738 · 被引用次数：56 · 研究领域：Mitochondrial Function and Pathology、ATP Synthase and ATPases Research、Trace Elements in Health

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 β- (GSK3 β- ) 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 β phosphorylation. Together, our results indicate that the AKT-GSK3 β signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT co...