日本生理学会大会発表要旨集
日本生理学会大会発表要旨集
セッションID: 2PHA-047
会議情報
虚血時の神経保護作用におけるHomerタンパクの分子機構について
*庄司 敏武藤 有子古市 貞一
著者情報
キーワード: Homer, postsynapse, apoptosis, ischemia
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Homer is an adaptor protein that exists in postsynapse and modulates the physiological functions of various proteins in neuron. Recently, it has been shown to be involved in some pathological conditions of brain, so that clinical significances of Homer tend to be increased.Our group has cloned Homer2 as one of the developmentally regulated gene in mouse cerebellum and clarified its basic features in mouse brain and some interesting roles at synapses. This time, we studied molecular mechanisms of Homer in neuronal apoptosis and ischemia.In biochemical and physiological studies of cerebellar granule cells, it was clarified that Homer modified the functions of NMDAR. While short form Homer is known to be an immediately early gene and work as a dominant negative form, it prevented apoptosis in cell level. These results indicated that Homer should adjust Ca2+ toxicity through NMDAR. Next, we investigated the molecular dynamics of Homer in brain ischemia, one of the most important diseases related to the neuronal apoptosis. In oxygen-glucose deprivation of hippocampal neurons, intrinsic cell protective mechanisms worked after ischemia, such as attenuation of interactions between Homer and other proteins, morphological changes of spines and so on. On the other hand, in the mouse brain ischemia model by occlusion of carotid arteries, the amounts of postsynaptic proteins were increased after reperfusion and enhancement of interactions between Homer and other proteins were observed. From these results, it is suggested that malfunctions of intrinsic cell protective mechanisms should become symptomatic exacerbating factors after brain ischemia. [J Physiol Sci. 2007;57 Suppl:S156]

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© 2007 日本生理学会
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