Magnolol Protects Osteoblastic MC3T3-E1 Cells Against Antimycin A-Induced Cytotoxicity Through Activation of Mitochondrial Function
- 429 Downloads
Antimycin A treatment of cells blocks the mitochondrial electron transport chain and leads to elevated ROS generation. In the present study, we investigated the protective effects of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells. Osteoblastic MC3T3-E1 cells were pre-incubated with magnolol before treatment with antimycin A. Cell viability and mineralization of osteoblasts were assessed by MTT assay and Alizarin Red staining, respectively. Mitochondrial dysfunction in cells was measured by mitochondrial membrane potential (MMP), complex IV activity, and ATP level. The cellular antioxidant effect of magnolol in osteoblastic MC3T3-E1 cells was assessed by measuring cardiolipin oxidation, mitochondrial superoxide levels, and nitrotyrosine content. Phosphorylated cAMP-response element-binding protein (CREB ) was evaluated using ELISA assay. Pretreatment with magnolol prior to antimycin A exposure significantly reduced antimycin A-induced osteoblast dysfunction by preventing MMP dissipation, ATP loss, and CREB inactivation. Magnolol also reduced cardiolipin peroxidation, mitochondrial superoxide, and nitrotyrosine production induced by antimycin A. These results suggest that magnolol has a protective effect against antimycin A-induced cell damage by its antioxidant effects and the attenuation of mitochondrial dysfunction. All these data indicate that magnolol may reduce or prevent osteoblast degeneration in osteoporosis or other degenerative disorders.
KEY WORDSmagnolol mitochondrial dysfunction MC3T3-E1 cells oxidative stress CREB
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20110005020).
- 14.Nicolson, G.L. 2007. Lipid replacement and antioxidant supplements to prevent membrane oxidation and restore mitochondrial function in metabolic syndrome and fatiguing illnesses. Townsend Letters 286: 112–120.Google Scholar
- 28.Wuthier, R.E., J.E. Chin, J.E. Hale, T.C. Register, L.V. Hale, and Y. Ishikawa. 1985. Isolation and characterization of calcium accumulating matrix vesicles from chondrocytes of chicken epiphyseal growth plate cartilage in primary culture. Journal of Biological Chemistry 260: 15972–15979.PubMedGoogle Scholar
- 31.Handschin, C., J. Rhee, J. Lin, P.T. Tarr, and B.M. Spiegelman. 2003. An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proceedings of the National Academy of Sciences of the United States of America 100: 7111–7116.PubMedCrossRefGoogle Scholar
- 33.Ryu, H., J. Lee, S. Impey, R.R. Ratan, and R.J. Ferrante. 2005. Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proceedings of the National Academy of Sciences of the United States of America 102: 13915–13920.PubMedCrossRefGoogle Scholar