BMB-3 Gene Expression, Epigenetic Marks, and Cellular Stress Changes Induced by High Vitamin B12
Abstract
Historically, deficiencies in Vitamin B12, or Cobalamin, have received a lot of attention in patients. Through routine testing, it has been noted that patients sometimes have high serum Vitamin B12, otherwise known as hypercobalaminemia (> 950 pg/mL) rather than a deficiency, which is widely ignored in the medical community. Transcobalamins (TCB types I and II) are required for the proper transportation and absorption of Vitamin B12 in the blood and liver cells. Studies indicate that most cases of hypercobalaminemia can be attributed to anomalies involving TCBs, specifically TCB II. Excessive Vitamin B12 levels induce production of TCB II antibodies that work to prevent absorption of Vitamin B12 by binding to it, which essentially puts a person in a low-Vitamin B12 state in their tissues. Therefore, high serum Vitamin B12 levels can be accompanied by functional symptoms of Vitamin B12 deficiencies, making it difficult to distinguish the two. Clinicians have no way to define or approach this issue specifically, as it is a relatively new discovery and research on the topic of hypercobalaminemia is scarce. Of the few available studies, some suggest that hypercobalaminemia may be implicated in poor prognosis of solid tumors and age-related cognitive deficits. Therefore, we sought to explore how hypercobalaminemia affects gene expression to determine why TCBs increase with high Vitamin B12 levels. To do this, we explored the epigenetic changes induced by hypercobalaminemia in a human neuronal cell line, SH-SY5Y cells. Through RT-qPCR, we determined miRNAs that were upregulated with high Vitamin B12, histone modifications to H3 and H4 that were significantly changed with high Vitamin B12, and an increase in superoxide dismutase activity with high Vitamin B12, indicating an increase in cellular stress. Though our study is still ongoing, our data indicates high Vitamin B12 levels stress the cells and induce important epigenetic changes that may lead to disease.
Keywords
Vitamin B12, epigenetics, gene expression, cellular stress
BMB-3 Gene Expression, Epigenetic Marks, and Cellular Stress Changes Induced by High Vitamin B12
University Readiness Center Greatroom
Historically, deficiencies in Vitamin B12, or Cobalamin, have received a lot of attention in patients. Through routine testing, it has been noted that patients sometimes have high serum Vitamin B12, otherwise known as hypercobalaminemia (> 950 pg/mL) rather than a deficiency, which is widely ignored in the medical community. Transcobalamins (TCB types I and II) are required for the proper transportation and absorption of Vitamin B12 in the blood and liver cells. Studies indicate that most cases of hypercobalaminemia can be attributed to anomalies involving TCBs, specifically TCB II. Excessive Vitamin B12 levels induce production of TCB II antibodies that work to prevent absorption of Vitamin B12 by binding to it, which essentially puts a person in a low-Vitamin B12 state in their tissues. Therefore, high serum Vitamin B12 levels can be accompanied by functional symptoms of Vitamin B12 deficiencies, making it difficult to distinguish the two. Clinicians have no way to define or approach this issue specifically, as it is a relatively new discovery and research on the topic of hypercobalaminemia is scarce. Of the few available studies, some suggest that hypercobalaminemia may be implicated in poor prognosis of solid tumors and age-related cognitive deficits. Therefore, we sought to explore how hypercobalaminemia affects gene expression to determine why TCBs increase with high Vitamin B12 levels. To do this, we explored the epigenetic changes induced by hypercobalaminemia in a human neuronal cell line, SH-SY5Y cells. Through RT-qPCR, we determined miRNAs that were upregulated with high Vitamin B12, histone modifications to H3 and H4 that were significantly changed with high Vitamin B12, and an increase in superoxide dismutase activity with high Vitamin B12, indicating an increase in cellular stress. Though our study is still ongoing, our data indicates high Vitamin B12 levels stress the cells and induce important epigenetic changes that may lead to disease.