Expression of hemoglobin in rodent neurons.
Hemoglobin is the major protein in red blood cells and transports oxygen from the lungs to oxygen-demanding tissues, like the brain. Mechanisms that facilitate the uptake of oxygen in the vertebrate brain are unknown. In invertebrates, neuronal hemoglobin serves as intracellular storage molecule for oxygen. Here, we show by immunohistochemistry that hemoglobin is specifically expressed in neurons of the cortex, hippocampus, and cerebellum of the rodent brain, but not in astrocytes and oligodendrocytes. The neuronal hemoglobin distribution is distinct from the neuroglobin expression pattern on both cellular and subcellular levels. Probing for low oxygen levels in the tissue, we provide evidence that hemoglobin alpha-positive cells in direct neighborhood with hemoglobin alpha-negative cells display a better oxygenation than their neighbors and can be sharply distinguished from those. Neuronal hemoglobin expression is upregulated by injection or transgenic overexpression of erythropoietin and is accompanied by enhanced brain oxygenation under physiologic and hypoxic conditions. Thus we provide a novel mechanism for the neuroprotective actions of erythropoietin under ischemic-hypoxic conditions. We propose that neuronal hemoglobin expression is connected to facilitated oxygen uptake in neurons, and hemoglobin might serve as oxygen capacitator molecule.
Schelshorn
Dominik W
DW
Division of Systems Physiology, Department of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
Schneider
Armin
A
Kuschinsky
Wolfgang
W
Weber
Daniela
D
Krüger
Carola
C
Dittgen
Tanjew
T
Bürgers
Heinrich F
HF
Sabouri
Fatemeh
F
Gassler
Nikolaus
N
Bach
Alfred
A
Maurer
Martin H
MH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000096:biosynthesis*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D006454:Hemoglobins; D009593:Nitroimidazoles; D011994:Recombinant Proteins; D004921:Erythropoietin; C033815:pimonidazole; D010100:Oxygen