Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

• Published in: Journal of Zhejiang University. B. Science 2006-02, Vol.7 (2), p.142-147
• Main Author: 韩义香 章圣辉 王西明 吴建波
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomedicine; Blotting, Western; Caspase 3; Caspases - metabolism; Cells; Cellular biology; Cerebellum - pathology; Cytochromes c - metabolism; Cytoplasm - metabolism; Deoxyribonucleic acid; DNA; DNA Fragmentation; Glucose - metabolism; Immunoblotting; Ischemia; Melatonin - metabolism; Melatonin - pharmacology; Membrane Potentials; Mitochondria - metabolism; Neurons - metabolism; Nitric Oxide Synthase Type I - metabolism; Oxygen - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Time Factors; 小脑粒细胞; 局部缺血再灌注; 抗细胞凋亡效应; 细胞色素c; 褪黑激素
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.2006.B0142

Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons （CGNs） by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation （OGD）. Results： The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential （its maximal protection ratio was 73.26%） and release of cytochrome c （its maximal inhibition ratio was 42.52%） and the subsequent activation of caspase-3 （its maximal protection ratio was 59.32%） in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion： Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfiusion.