Influence of mitochondrial deficiency on expression of microtubule-associated proteins in primary cultured hippocampal neurons of neonatal rats |
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Authors: | ZHANG La AN Wen-li LI Li XUE Bin BAN Li-qin LI Xiao-ming XU Yan-lin LIU Shu-sen |
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Affiliation: | 1.Xuanwu Hospital of Capital University of Medical Sciences, Beijing Key Laboratory for Brain Aging, Beijing 100053, China;2.Institute of Zoology, Chinese Academy of Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing 100080, China |
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Abstract: | AIM: In order to study the relationship between mitochondrial deficiency and Alzheimer's disease(AD), we used sodium azide, a specific inhibitor of cytochrome C oxidase (COX), to develop a cell model of mitochondrial complex IV deficiency and investigated the impairment of microtubules and microtubule-associated proteins. METHODS: Primary cultured hippocampal neurons of hewborn rats were exposed to sodium azidethen cell viability was measured by MTT method; cell morphology, immunofluorecence-stained cellular microtubules and microtubule-associated proteins were observed by confocal microscopy. RESULTS: Primary cultured hippocampal neurons were exposed to 8-128 mmol/L sodium azide for 3-24 h, MTT absorbance decreased dose-and time-dependently. Exposed to 64 mmol/L sodium azide for 6 h, the processes of cells retracted, synapses disappeared, axons were shortened under contrast microscope. Meanwhile, microtubles were disassembled and became disorderly, the expression of microtubule-associated proteins were also reduced especially in the processes observed by confocal microscopy. CONCLUSION: Sodium azide inhibits the assembly and polymerization of tubulin in microtubules which may be reduced by low expression of microtubule-associated proteins in nerve cells. The damage of axons induced by microtubule collapse further blocks the intercellular signal transduction and intracellular material transportation which are important causes in cell death. |
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Keywords: | Microtubule-associated proteins Hippocampus Neurons Mitochondria Alzheimer's disease |
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