TY - JOUR
T1 - Hemoglobin is present as a canonical α2β2 tetramer in dopaminergic neurons
AU - Russo, Roberta
AU - Zucchelli, Silvia
AU - Codrich, Marta
AU - Marcuzzi, Federica
AU - Verde, Cinzia
AU - Gustincich, Stefano
N1 - Funding Information:
We are indebted to all the members of the SG lab for thought-provoking discussions and to Cristina Leonesi for technical support. This work was supported by the Italian Ministry of Education, University and Research (FIRB grant prot. RBAP11FRE9 ) and by the European Territorial Cooperation program for Italy-Slovenia cross-border cooperation 2007–2013 (MINA, CUP D35C12002830003 ) to S.G. and by the Italian National Programme for Antarctic Research (PNRA) to C.V.
PY - 2013
Y1 - 2013
N2 - 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 64 kDa; (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.
AB - 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 64 kDa; (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.
KW - Dopaminergic neurons
KW - Hemoglobin
KW - Mouse
KW - Native structure
UR - http://www.scopus.com/inward/record.url?scp=84884646240&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2013.05.005
DO - 10.1016/j.bbapap.2013.05.005
M3 - Article
SN - 1570-9639
VL - 1834
SP - 1939
EP - 1943
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 9
ER -