| Autor: |
W J, Cai, Y, Chen, L X, Shi, H R, Cheng, I, Banda, Y H, Ji, Y T, Wang, X M, Li, Y X, Mao, D F, Zhang, P P, Dai, X Y, Sun, X H, Ning, S B, Huang, J F, Ma, S F, Zhao |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Oxidative Medicine and Cellular Longevity |
| ISSN: |
1942-0994 |
| Popis: |
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 3β- (GSK3β-) 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 GSK3β phosphorylation. Together, our results indicate that the AKT-GSK3β 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text