AKT-GSK3ß Signaling Pathway Regulates Mitochondrial Dysfunction-Associated OPA1 Cleavage Contributing to Osteoblast Apoptosis: Preventative Effects of Hydroxytyrosol.
Oxid Med Cell Longev
; 2019: 4101738, 2019.
Article
in En
| MEDLINE
| ID: mdl-31281574
ABSTRACT
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 3ß- (GSK3ß-) 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 GSK3ß phosphorylation. Together, our results indicate that the AKT-GSK3ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoblasts
/
Osteoporosis
/
Phenylethyl Alcohol
/
Proto-Oncogene Proteins c-akt
/
Glycogen Synthase Kinase 3 beta
/
GTP Phosphohydrolases
/
Mitochondria
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Oxid Med Cell Longev
Journal subject:
METABOLISMO
Year:
2019
Document type:
Article
Affiliation country: