Russo Roberta, Zucchelli Silvia, Codrich Marta, Marcuzzi Federica, Verde Cinzia, Gustincich Stefano
Institute of Protein Biochemistry, CNR, Via Pietro Castellino 111, Naples, Italy.
Biochim Biophys Acta. 2013 Sep;1834(9):1939-43. doi: 10.1016/j.bbapap.2013.05.005. Epub 2013 May 17.
Hemoglobin is the oxygen carrier in blood erythrocytes. Oxygen coordination is mediated by α2β2 tetrameric structure via binding of the ligand to the heme iron atom. This structure is essential for hemoglobin function in the blood. In the last few years, expression of hemoglobin has been found in atypical sites, including the brain. Transcripts for α and β chains of hemoglobin as well as hemoglobin immunoreactivity have been shown in mesencephalic A9 dopaminergic neurons, whose selective degeneration leads to Parkinson's disease. To gain further insights into the roles of hemoglobin in the brain, we examined its quaternary structure in dopaminergic neurons in vitro and in vivo. Our results indicate that (i) in mouse dopaminergic cell line stably over-expressing α and β chains, hemoglobin exists as an α2β2 tetramer; (ii) similarly to the over-expressed protein, endogenous hemoglobin forms a tetramer of 64kDa; (iii) hemoglobin also forms high molecular weight insoluble aggregates; and (iv) endogenous hemoglobin retains its tetrameric structure in mouse mesencephalon in vivo. In conclusion, these results suggest that neuronal hemoglobin may be endowed with some of the biochemical activities and biological function associated to its role in erythroid cells. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.
血红蛋白是血液红细胞中的氧载体。氧的配位作用是通过配体与血红素铁原子结合，由α2β2四聚体结构介导的。这种结构对于血红蛋白在血液中的功能至关重要。在过去几年中，已发现在包括大脑在内的非典型部位有血红蛋白表达。在中脑A9多巴胺能神经元中已显示出血红蛋白α链和β链的转录本以及血红蛋白免疫反应性，这些神经元的选择性变性会导致帕金森病。为了进一步深入了解血红蛋白在大脑中的作用，我们在体外和体内研究了多巴胺能神经元中血红蛋白的四级结构。我们的结果表明：（i）在稳定过表达α链和β链的小鼠多巴胺能细胞系中，血红蛋白以α2β2四聚体形式存在；（ii）与过表达的蛋白质类似，内源性血红蛋白形成64kDa的四聚体；（iii）血红蛋白还形成高分子量不溶性聚集体；（iv）内源性血红蛋白在小鼠中脑体内保留其四聚体结构。总之，这些结果表明神经元血红蛋白可能具有与其在红细胞中的作用相关的一些生化活性和生物学功能。本文是名为：氧结合与传感蛋白的特刊的一部分。
