Effect of (m)VD-hemopressin against A beta 1-42-induced oxidative stress and apoptosis in mouse hippocampal neurons

摘要

Alzheimer's disease (AD) is a serious neurodegenerative disease. Senile plaques (SPs) composed of amyloid-beta (A beta) are typical features of AD. A beta plays a key role in the disease and has the ability to induce other pathological characteristics of AD, including oxidative stress injury. (m)VD-hemopressin (VD), a peptide derived from mouse brain extracts, can bind cannabinoid 1 receptor (CB1R) as an agonist. Our previous report indicated that VD reverses memory impairment induced by A beta 1-42 in mice. This study aimed to clarify the mechanism by which VD protects hippocampal neurons against A beta 1-42-induced impairment. Our results showed that VD inhibited oxidative stress injury induced by A beta 1-42, as demonstrated by the VD-induced reversal of the upregulation of reactive oxygen species (ROS) and the intracellular lipid peroxidation product malondialdehyde (MDA) and the downregulation of the activities of the antioxidative enzymes catalase (CAT) and glutathione peroxidase (GSHPX) in mouse hippocampal neurons. We also found that VD restored the decrease in cell growth and viability induced by A beta 1-42 and reversed A beta 1-42-induced apoptosis mediated by the apoptosis-associated proteins Bcl-2 and Bax. However, cotreatment with AM251 (an antagonist of CB1R) blocked the effects of VD. In brief, this study suggested that through CB1R, VD reversed the impairment of cell growth and viability, oxidative stress injury and apoptosis induced by A beta 1-42. Therefore, VD may be a promising agent for the treatment of diseases that involve oxidative stress injury and apoptosis induced by A beta 1-42, such as AD.