Neuronal Hemoglobin Expression and Its Relevance to Multiple Sclerosis Neuropathology

• Published in: Journal of molecular neuroscience Vol. 59; no. 1; pp. 1 - 17
• Main Authors: Brown, Nolan, Alkhayer, Kholoud, Clements, Robert, Singhal, Naveen, Gregory, Roger, Azzam, Sausan, Li, Shuo, Freeman, Ernest, McDonough, Jennifer
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2016; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; ATP Synthetase Complexes - metabolism; beta-Globins - genetics; beta-Globins - metabolism; Biomedical and Life Sciences; Biomedicine; Brain; Carbon dioxide; Case-Control Studies; Cell Biology; Cell Line, Tumor; Cell Nucleus - metabolism; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Chromatography; Female; Hemoglobin; Histone Demethylases - metabolism; Histones - metabolism; Humans; Male; Mass spectrometry; Metabolism; Middle Aged; Mitochondria; Mitochondria - metabolism; Multiple sclerosis; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Neurochemistry; Neurology; Neuropathology; Neurosciences; Proteomics; Pyramidal Cells - metabolism; Scientific imaging; United States > US; Hemoglobin expression; Multiple sclerosis; Mitochondrial genes; Pyramidal neurons; Histone methylation; Mass spectrometry
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0711-6

Multiple sclerosis (MS) is characterized by demyelination and progressive neurological disability. Previous studies have reported defects to mitochondria in MS including decreased expression of nuclear encoded electron transport chain subunit genes and inhibition of respiratory complexes. We previously reported increased levels of the hemoglobin β subunit (Hbb) in mitochondrial fractions isolated from postmortem MS cortex compared to controls. In the present study, we performed immunohistochemistry to determine the distribution of Hbb in postmortem MS cortex and identified proteins which interact with Hbb by liquid chromatography tandem mass spectrometry (LC-MS/MS). We found that Hbb was enriched in pyramidal neurons in internal layers of the cortex and interacts with subunits of ATP synthase, histones, and a histone lysine demethylase. We also found that Hbb is present in the nucleus and that expression of Hbb in SH-SY5Y neuroblastoma cells increased trimethylation of histone H3 on lysine 4 (H3K4me3), a histone mark that regulates cellular metabolism. These data suggest that Hbb may be a part of a mechanism linking neuronal energetics with epigenetic changes to histones in the nucleus and may provide neuroprotection in MS by supporting neuronal metabolism.