机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, People’s Republic of China[2]The Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, People’s Republic of China[3]The Cecile Cox Quillen Laboratory of Geriatric Research, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA[4]Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.
基金：
This study was supported by Grants 81071095,
81120108011, and 81361128010 (to XX) from the National Natural
Science Foundation of China, the Grant CCI-132567 from Canadian
Institutes of Health Research (CIHR, to KJ), Suzhou Science and
Technology Development Program (SZS201205), and the Priority
Academic Program Development of Jiangsu Higher Education Institutions
of China (to XX).
第一作者机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, People’s Republic of China[2]The Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou 215123, Jiangsu, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu, People’s Republic of China
