Unexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells

被引:211
作者
Biagioli, Marta [1 ,2 ]
Pinto, Milena [1 ]
Cesselli, Daniela [4 ]
Zaninello, Marta [1 ]
Lazarevic, Dejan [1 ,2 ,3 ]
Roncaglia, Paola [1 ]
Simone, Roberto [1 ,2 ]
Vlachouli, Christina [1 ]
Plessy, Charles [5 ]
Bertin, Nicolas [5 ]
Beltrami, Antonio [4 ]
Kobayashi, Kazuto [6 ]
Gallo, Vittorio [7 ]
Santoro, Claudio [8 ]
Ferrer, Isidro [9 ]
Rivella, Stefano [10 ]
Beltrami, Carlo Alberto [4 ]
Carninci, Piero [5 ]
Raviola, Elio [11 ]
Gustincich, Stefano [1 ,2 ]
机构
[1] AREA Sci Pk, Int Sch Adv Studies, Sector Neurobiol, I-34012 Trieste, Italy
[2] AREA Sci Pk, Giovanni Armenise Harvard Fdn Lab, I-34012 Trieste, Italy
[3] AREA Sci Pk, Consorzio Ctr Biomed Mol, I-34012 Trieste, Italy
[4] Univ Udine, Ctr Interdipartimentale Med Rigenerat, I-33100 Udine, Italy
[5] RIKEN, Om Sci Ctr, Yokohama Inst, Tsurumi Ku, Kanagawa 2300045, Japan
[6] Fukushima Med Univ, Sch Med, Dept Mol Genet, Fukushima 9601295, Japan
[7] Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA
[8] Univ Piemonte Orientale, Dept Med Sci, I-28100 Novara, Italy
[9] Univ Barcelona, Univ Hosp Bellvitge, Inst Invest Biomed Bellvitge, Inst Neuropathol, Lhospitalet De Llobregat 08907, Spain
[10] Cornell Univ, Weill Med Coll, Dept Pediat Hematol Oncol, New York, NY 10021 USA
[11] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
关键词
astrocytes; hemoglobin; oligodendrocytes; oxidative phosphorylation; Parkinson; PARKINSONS-DISEASE; GENE-EXPRESSION; HEMOGLOBIN; BRAIN; MIDBRAIN; PROTEIN; MOUSE; VULNERABILITY; MECHANISMS; INJURY;
D O I
10.1073/pnas.0813216106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:15454 / 15459
页数:6
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