The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus.
The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus.
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DOI：
10.18632/oncotarget.10380
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Yen K
中科院分区：
文献类型：
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作者：
Kim SJ;Guerrero N;Wassef G;Xiao J;Mehta HH;Cohen P;Yen K
Humanin是由线粒体基因组编码的一种分泌型小肽。Humanin及其类似物在多种年龄相关疾病中具有保护作用，包括2型糖尿病和阿尔茨海默病，通过体外和体内的细胞保护和神经保护作用。然而，人蛋白介导的信号通路还没有得到很好的理解。在本文中，我们证明了humanin通过GP 130/IL 6ST受体复合物激活AKT，ERK 1/2和STAT 3信号通路。Humanin处理增加AKT、ERK 1/2和STAT 3中的磷酸化，其中PI 3 K、MEK和JAK分别参与这三种信号传导途径的激活。此外，老年小鼠，而不是年轻的小鼠，注射humanin显示在海马AKT和ERK 1/2磷酸化的增加。这些发现揭示了人蛋白的关键信号通路，这对人蛋白的功能很重要，并且还证明了大脑区域中的年龄特异性体内效应，该区域对年龄依赖性方式的记忆形成至关重要。
Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age-specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner.