Hemoglobin is present as a canonical α2β2 tetramer in dopaminergic neurons

Abstract

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.

Hemoglobin-Improved Protection in Cultured Cerebral Cortical Astroglial Cells: Inhibition of Oxidative Stress and Caspase Activation

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Hemoglobin: a Gas Transport Molecule That Is Hormonally Regulated in the Ovarian Follicle in Mice and Humans1

“…These include roles in sequestering NO, neutralizing reactive oxygen species (ROS), protection from apoptosis, regulation of signal transduction and iron metabolism, lipid metabolism, and a suggested role in hydrogen sulfide turnover. Local production of hemoglobin has been detected in the brain, lungs, kidney, immune system, vascular endothelial system, and female reproductive system, as well as in cancer cells [16][17][18][19][20][21][22][23][24][25][26].…”

Hemoglobin Expression in Nonerythroid Cells: Novel or Ubiquitous?

“…Russo et al [26] further extended their study and showed that Hb is present as α 2 β 2 tetramer when overexpressed in dopaminergic MN9D cell line. They suggested that neuronal Hb may retain some of the biochemical activities and biological functions of Hb of erythroid lineage laying down the foundation for a better understanding of its role in brain physiology and in neurodegenerative diseases.…”