Ac-cel, a Novel Antioxidant, Protects Against Hydrogen Peroxide-induced Injury in PC12 Cells via Attenuation of Mitochon
- PDF / 585,631 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 112 Downloads / 159 Views
Ac-cel, a Novel Antioxidant, Protects Against Hydrogen Peroxide-induced Injury in PC12 Cells via Attenuation of Mitochondrial Dysfunction Xianjun Guo & Yuting Chen & Qunfang Liu & Jian Wu & Luoyi Wang & Xican Tang & Weimin Zhao & Haiyan Zhang
Received: 24 November 2012 / Accepted: 7 January 2013 / Published online: 24 January 2013 # Springer Science+Business Media New York 2013
Abstract Oxidative stress has been implicated in pathophysiology of many neurodegenerative diseases (ND) and increased oxidative stress is closely associated with mitochondrial dysfunction. As a result, looking for potent antioxidants, especially those targeting mitochondria, has become an attractive strategy in ND therapy. In this study, we explored protective effects and potential mechanism of Ac-cel, a novel compound, against hydrogen peroxide (H2O2)-induced injury in PC12 cells. Pretreatment of PC12 cells with Ac-cel prior to 24 h of H2O2 exposure markedly attenuated cytotoxicity induced by H2O2 as evidenced by morphological changes and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Ac-cel also exhibited potent antiapoptotic effect demonstrated by results of annexin V and PI staining. The above beneficial effects of Ac-cel were accompanied by improved mitochondrial function, reduced caspase-3 cleavage as well as upregulated ratio of Bcl-2/Bax protein expression. Moreover, Ac-cel pretreatment markedly reversed intracellular reactive oxygen species (ROS) accumulation following 30 min of H2O2 exposure in PC12 cells. Further, subcellular investigation indicated that Ac-cel significantly reduced production of mitochondrial ROS in isolated rat cortical
Xianjun Guo and Yuting Chen contribute equally to this work. X. Guo : Y. Chen : Q. Liu : J. Wu : L. Wang : X. Tang : W. Zhao (*) : H. Zhang (*) State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People’s Republic of China e-mail: [email protected] e-mail: [email protected]
mitochondria. Taken together, the present study, for the first time, reports that Ac-cel pretreatment inhibits H2O2-stimulated early accumulation of intracellular ROS possibly via reducing mitochondrial ROS production directly and leads to subsequent preservation of mitochondrial function. These results indicate that Ac-cel is a potential drug candidate for treatment of oxidative stress-associated ND. Keywords Apoptosis . Antioxidant . Hydrogen peroxide . Mitochondria . Neuroprotection . Reactive oxygen species Abbreviations CNS Central nervous system DCF-DA 2, 7-Dichlorofluorescein diacetate DMEM Dulbecco's modified Eagle's medium DMSO Dimethylsulfoxide H2O2 Hydrogen peroxide MMP Mitochondrial membrane potential MPTP Mitochondrial permeability transition pore MTT 3-(4,5-Dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide NCS Newborn calf serum ND Neurodegenerative diseases PC12 Pheochromocytoma PI Propidium iodide ROS Reactive oxygen species SD Sprague–Dawley Introdu
Data Loading...