Protective effect of melatonin on neurons after oxidative-stress injury
- Author:
- No author available
- Journal Title:
- NEURAL REGENERATION RESEARCH
- Issue:
- 7
- DOI:
- No doi available
- Key Word:
- No keyword available
Abstract： BACKGROUND: It has been suggested that melatonin(MT) can protect secondary neuronal injury.However,the protective effect of MT on neuronal injury in ischemia/reperfusion models in vitro still has not been proved.OBJECTIVE:To investigate the protective effect of MT on central ischemic injury of nerve cells and analyze its possible mechanism.DESIGN: Contrast observational study.SETTING: Department of Biochemistry and Molecular Biology,Tongji Medical College,Huazhong University of Science and Technology.MATERIALS: Rats aged 7-8 days and weighing 10-12g were provided by Medical Experimental Animal Center,Tongji Medical College,Huazhong University of Science and Technology,MT was provided by Sigma Company,USA.METHODS:The experiment was carried out in the Laboratory of Biochemistry and Molecular Biology,Tongji Hospital,Huazhong University of Science and Technology from October 2002 to March 2004.The effects of MT on the neurodegeneration induced by oxygen-glucose-deprivation (OGD) were tested in cultured rat cerebellar granule cells.Neuron damage was quantitatively assessed by Typan Blue exclusion and MTT assay at different time points after oxygen-glucose-deprivation(90 minutes).DNA gel electrophoresis and acridine orange stain were performed to determine the nature of cell damage.And fluorescence spectrophotometer was used for quantification of intracellular malondialdehyde(MDA)at various time intervals.MAIN OUTCOME MEASURES: Correlation between degrees of neuronal injury and reperfusion times,apoptosis,and production of MDA in cells.RESULTS:①The neuron injury was aggravated with reperfusion time.②The protective effect of MT was time-and dose-dependent when its concentration was not higher than 10 μmol/L.⑧When neurons were exposed to OGD for 90 minutes.part of the cells exhibited typical features of apoptosis:internucleosomal DNA condensation and DNA ladder on agarose gel electrophoresis.MT added to cells recovering from OGD exerted neuroprotective action against OGD-induced apoptosis.④In OGD exposed cultures,the production of MDA burst 12 hours after OGD,while MT significantly decreased the generation of MDA(P＜0.05)in a time-dependent manner.CONCLUSION: MT may have therapeutic potential in the prevention and treatment of ischemic/hypoxic neuronal damage,and this neuroprotective action may contribute to the antioxidant nature of MT.
- [1]HAN Yi-xiang,ZHANG Sheng-Hui,WANG Xi-ming,etc.Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion[J].2006,(2).
- [2]段秋红,王西明,王忠强,等.Role of Mitochondria in Neuron Apoptosis during Ischemia-Reperfusion Injury[J].2004,(5).
- [3]R T, Cheung.Cerebrovascular disease--advances in management.[J].2001,7(1).
- [4]Mackenzie A,Robertson GS,Thompson C,etc.Kainic acid-induced naip expression in the hippocampus is blocked in mice lacking TNF receptors.[J].2004,123(1).
- [5]G M, Yan,R P, Irwin,S Z, Lin,etc.Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons.[J].1995,274(2).
- [6]Bras M.,Queenan B.,Susin S. A..Programmed cell death via mitochondria: Different modes of dying[J].2005,70(2).
- [7]Klas Blomgren,Changlian Zhu,Ulrika Hallin,etc.Mitochondria and ischemic reperfusion damage in the adult and in the developing brain[J].2003,304(3).
- [8]T, Mosmann.Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.[J].1983,65(1-2).
- [9]Jaako K,Kaasik A,Kalda A,etc.Dehydroepiandrosterone sulphate prevents oxygen-glucose deprivation-induced injury in cerebellar granule cell culture.[J].2001,102(2).
- [10]Kalda A,Zharkovsky A.Metabotropic glutamate receptor agonists protect from oxygen-glucose deprivation- and colchicine-induced apoptosis in primary cultures of cerebellar granule cells.[J].1999,92(1).
- [11]Gjumrakch Aliev,Mark A. Smith,George Perry,etc.Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer's disease[J].2004,4(5).
- [12]Huang F,Schneider JS,Vemuri MC.Modulation of ATP levels alters the mode of hydrogen peroxide-induced cell death in primary cortical cultures: effects of putative neuroprotective agents.[J].2004,997(1).
- [13]W M H Behan,M McDonald,L G Darlington,etc.Oxidative stress as a mechanism for quinolinic acid‐induced hippocampal damage: protection by melatonin and deprenyl[J].1999,128(8).
- [14]翁玉椿,王秀平,卢泳才,等.细胞和细胞膜内过氧化脂质的微量定量[J].1985,(3).
- [15]Gu Z,Nakamura T,Yao D,etc.Nitrosative and oxidative stress links dysfunctional ubiquitination to Parkinson's disease[J].2005,12(9).
- [16]Furuichi T,Liu W,Liu KJ,etc.Generation of hydrogen peroxide during brief oxygen-glucose deprivation induces preconditioning neuronal protection in primary cultured neurons.[J].2005,79(6).
- [17]V, Gallo,M T, Ciotti,A, Coletti,etc.Selective release of glutamate from cerebellar granule cells differentiating in culture.[J].1982,79(24).
- [18]Graciela Letechipı́a-Vallejo,Ignacio González-Burgos,Miguel Cervantes.Neuroprotective Effect of Melatonin on Brain Damage Induced by Acute Global Cerebral Ischemia in Cats[J].2001,32(3).
- [19]Serra PA,Migheli R,Miele E,etc.Endogenous melatonin protects L-DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L-DOPA therapy in Parkinson's disease.[J].2006,40(3).
- [20]Zhang, C.,Shen, W.,Zhang, G..N-methyl-d-aspartate receptor and L-type voltage-gated Ca2+ channel antagonists suppress the release of cytochrome c and the expression of procaspase-3 in rat hippocampus after global brain ischemia[J].2002,328(3).
- [21]Onteniente B,Couriaud C,Braudeau J,etc.The mechanisms of cell death in focal cerebral ischemia highlight neuroprotective perspectives by anti-caspase therapy.[J].2003,66(8).
- [22]Yulug B,Reiter RJ,Hermann DM,etc.Melatonin reduces disseminate neuronal death after mild focal ischemia in mice via inhibition of caspase-3 and is suitable as an add-on treatment to tissue-plasminogen activator.[J].2004,36(3).
- [23]Sun L,Xu Z,Yu X,etc.Investigation of the neuronal death mode induced by glutamate treatment in serum-, antioxidant-free primary cultured cortical neurons.[J].2003,145(2).
- [24]Anna Colell,Carmen Garcı́a-Ruiz,Montserrat Mari,etc.Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol‐regulated membrane fluidity[J].2004,560(1-3).