Neuronal Hemoglobin Expression and Its Relevance to Multiple Sclerosis Neuropathology

J Mol Neurosci. 2016 May;59(1):1-17. doi: 10.1007/s12031-015-0711-6. Epub 2016 Jan 25.


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.

Keywords: Hemoglobin expression; Histone methylation; Mass spectrometry; Mitochondrial genes; Multiple sclerosis; Pyramidal neurons.

MeSH terms

  • ATP Synthetase Complexes / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Female
  • Histone Demethylases / metabolism
  • Histones / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Pyramidal Cells / metabolism*
  • beta-Globins / genetics
  • beta-Globins / metabolism*


  • Histones
  • beta-Globins
  • Histone Demethylases
  • ATP Synthetase Complexes