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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Neuronal Hemoglobin Expression and Its Relevance to Multiple Sclerosis Neuropathology
Nolan Brown1, Kholoud Alkhayer1, Robert Clements1
1Department of Biological Sciences and School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA.
Abstract:
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.
Insights
Hemoglobin beta subunit (Hbb) is found in the nucleus of brain cells in multiple sclerosis (MS). Hbb interacts with histones, potentially linking neuronal energy to epigenetic regulation and offering neuroprotection in MS.
Area of Science:
- Neuroscience
- Cell Biology
- Epigenetics
Background:
- Multiple sclerosis (MS) involves demyelination and neurological decline.
- Mitochondrial dysfunction, including impaired respiratory complexes, is observed in MS.
- Previous research indicated elevated hemoglobin beta subunit (Hbb) in MS brain mitochondria.
Purpose of the Study:
- To investigate the distribution and nuclear localization of Hbb in postmortem MS cortex.
- To identify proteins interacting with Hbb in MS brain tissue.
- To explore the functional role of Hbb in neuronal metabolism and epigenetic regulation.
Main Methods:
- Immunohistochemistry was used to determine Hbb distribution in postmortem MS cortical tissue.
- Liquid chromatography tandem mass spectrometry (LC-MS/MS) identified Hbb-interacting proteins.
- Experiments in SH-SY5Y neuroblastoma cells assessed the impact of Hbb expression on histone modifications.
Main Results:
- Hbb was found enriched in pyramidal neurons within internal cortical layers.
- Hbb interacts with ATP synthase subunits, histones, and a histone lysine demethylase.
- Nuclear presence of Hbb correlated with increased histone H3 lysine 4 trimethylation (H3K4me3) in neuroblastoma cells.
Conclusions:
- Hbb is present in the nucleus of neurons in MS cortex and interacts with key cellular components.
- Hbb may link neuronal energy metabolism with epigenetic modifications.
- These findings suggest a potential neuroprotective role for Hbb in MS by supporting neuronal metabolism.
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