期刊
NEUROSCIENCE
卷 143, 期 1, 页码 165-173出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.07.055
关键词
insulin; insulin receptor; ischemia; oxygen-glucose deprivation; cultured neurons
Curiosity surrounding the physiological relevance of neural insulin signaling has gradually developed since the discovery that nervous tissue contains both the hormone and its receptor. Similar to other receptor tyrosine kinases, ligand interaction with the insulin receptor (IR) activates a variety of intracellular signaling pathways, particularly those relevant to cellular survival. Consequently, one explanation for the presence of the insulin pathway in the brain may involve participation in the response to neuronal injury. To investigate this possibility, the present study began by examining the effect of oxygen-glucose deprivation (OGD), a well-characterized in vitro model of ischemia, on ligand-binding, surface expression, and function of the IR in cultured rat neurons that were prepared under serum-free conditions. Reduced insulin-binding was observed following OGD, although surface expression of the receptor was not altered. However, OGD did significantly decrease the ability of insulin to stimulate phosphorylation of the transmembrane IR beta-subunit, Without affecting protein expression of this subunit. Subsequent experiments focused on the manner in which pharmacologically manipulating IR function affected neuronal viability after OGD. Application of the IR sensitizer metformin moderately improved neuronal viability, while the specific IR tyrosine kinase inhibitor tyrphostin A47 was able to dramatically decrease viability; both compounds acted without affecting IR surface expression. Our study suggests that not only does the IR appear to play an important role in neuronal survival, but also that neurons may actively maintain IRs on the cell surface to compensate for the OGD-induced decrease in the ability of insulin to phosphorylate its receptor. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据