Unexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells
Unexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells
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DOI：
10.1073/pnas.0813216106
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发表时间：
2009-09-08
影响因子：
11.1
通讯作者：
Gustincich, Stefano
中科院分区：
文献类型：
--
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
中脑多巴胺能（mDA）细胞系统由黑质（SN）（A9神经元）和腹侧被盖区（VTA）（A10细胞）中的两组主要投射细胞组成。A9神经元形成黑质纹状体通路，并参与调节随意运动和姿势反射。它们的选择性退化导致帕金森病。在这里，我们报告，A9多巴胺能神经元（DA）的基因表达分析确定的α和β链的血红蛋白（Hb）的转录本。珠蛋白免疫反应性装饰大多数A9 DA，皮质和海马星形胶质细胞和成熟的少突胶质细胞的亚群。这种表达模式在不同的小鼠品系以及大鼠和人中得到证实。我们发现，血红蛋白表达在人死后的大脑SN。通过对多巴胺能细胞系过表达α-和β-珠蛋白链的微阵列分析，观察到参与O-2稳态和氧化磷酸化的基因的变化，将Hb表达与线粒体功能联系起来。我们的数据表明，最著名的携氧球蛋白并不局限于血液，但它可能在大脑和神经退行性疾病的正常生理中发挥作用。
The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the substantia nigra (SN) (A9 neurons) and the ventral tegmental area (VTA) (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson's disease. Here, we report that gene expression analysis of A9 dopaminergic neurons (DA) identifies transcripts for alpha- and beta-chains of hemoglobin (Hb). Globin immunoreactivity decorates the majority of A9 DA, a subpopulation of cortical and hippocampal astrocytes and mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains and in rat and human. We show that Hb is expressed in the SN of human postmortem brain. By microarray analysis of dopaminergic cell lines overexpressing alpha- and beta-globin chains, changes in genes involved in O-2 homeostasis and oxidative phopshorylation were observed, linking Hb expression to mitochondrial function. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain and neurodegenerative diseases.