NS-3 To B12 or Not to B12: How High Serum B12 Affects Oxidative Stress in Neural Cells
SCURS Disciplines
Cell Biology
Document Type
Oral Presentation
Abstract
Low Vitamin B12 (“B12”) and its physiological effects have been widely studied. Contrarily, there is very little known and understood about high serum B12 and the roles it could play in diagnosing serious diseases like cognitive decline. Excessive levels of B12 in the serum, measured at two times the medical “normal” level, are linked to solid tumors and a poor prognosis in cancer. Increased B12 levels induce production of transcobalamin antibodies, which target B12 within tissues, leaving them deficient. Other published research and anecdotal evidence points to a link between high B12 and cognitive deficit/decline. Therefore, we sought to determine if B12 doses at a 2x level would affect gene expression in a human neuronal cell line. In the Summer of 2023, our lab investigated the expression of 95 miRNAs in SH-SY5Y cells that were exposed to control conditions or 2x B12 (cobamamide). Four miRNAs were significantly increased with elevated B12. MiRNAs affect gene expression by targeting mRNA for degradation, and as a result, miRNA targets would theoretically be reduced. We analyzed the four miRNAs’ targets (gene ontology) and found that just over 40 genes are involved in combating oxidative stress. An ELISA performed previously in our lab showed elevated reactive oxygen species in the 2x B12-treated cells. Therefore, we further investigated the impact of the 2x B12 treatment on oxidative stress through conducting qPCR array panels for oxidative stress-related genes. Since B12 caused an increase in 4 miRNAs, we anticipated that expression of target genes would decrease. We grew SH-SY5Y cells and treated with either fed control culture medium or culture medium supplemented with 2x their regular B12 in the form of cobamamide, which is a synthetic form of B12 that is added to grains, drinks, and other fortified foods. After 48 hours, we isolated RNA, synthesized cDNA, and performed qPCR arrays for oxidative stress. Our initial data indicated 15 genes were significantly downregulated in the 2x B12-treated cells. We are currently using individual Taqman assays to validate our findings. Our knowledge from this study may have broad effects on human health regarding the clinical significance of elevated serum B12. Further investigation into complete physiological systems is required, given the intricate nature of B12 absorption in the gut, novel insights into B12 storage within the body, and the transcobalamin antibodies generated in response to elevated Vitamin B12.
Keywords
Vitamin B12, epigenetics, gene expression, oxidative stress
Start Date
11-4-2025 2:55 PM
Location
CASB 117
End Date
11-4-2025 3:10 PM
NS-3 To B12 or Not to B12: How High Serum B12 Affects Oxidative Stress in Neural Cells
CASB 117
Low Vitamin B12 (“B12”) and its physiological effects have been widely studied. Contrarily, there is very little known and understood about high serum B12 and the roles it could play in diagnosing serious diseases like cognitive decline. Excessive levels of B12 in the serum, measured at two times the medical “normal” level, are linked to solid tumors and a poor prognosis in cancer. Increased B12 levels induce production of transcobalamin antibodies, which target B12 within tissues, leaving them deficient. Other published research and anecdotal evidence points to a link between high B12 and cognitive deficit/decline. Therefore, we sought to determine if B12 doses at a 2x level would affect gene expression in a human neuronal cell line. In the Summer of 2023, our lab investigated the expression of 95 miRNAs in SH-SY5Y cells that were exposed to control conditions or 2x B12 (cobamamide). Four miRNAs were significantly increased with elevated B12. MiRNAs affect gene expression by targeting mRNA for degradation, and as a result, miRNA targets would theoretically be reduced. We analyzed the four miRNAs’ targets (gene ontology) and found that just over 40 genes are involved in combating oxidative stress. An ELISA performed previously in our lab showed elevated reactive oxygen species in the 2x B12-treated cells. Therefore, we further investigated the impact of the 2x B12 treatment on oxidative stress through conducting qPCR array panels for oxidative stress-related genes. Since B12 caused an increase in 4 miRNAs, we anticipated that expression of target genes would decrease. We grew SH-SY5Y cells and treated with either fed control culture medium or culture medium supplemented with 2x their regular B12 in the form of cobamamide, which is a synthetic form of B12 that is added to grains, drinks, and other fortified foods. After 48 hours, we isolated RNA, synthesized cDNA, and performed qPCR arrays for oxidative stress. Our initial data indicated 15 genes were significantly downregulated in the 2x B12-treated cells. We are currently using individual Taqman assays to validate our findings. Our knowledge from this study may have broad effects on human health regarding the clinical significance of elevated serum B12. Further investigation into complete physiological systems is required, given the intricate nature of B12 absorption in the gut, novel insights into B12 storage within the body, and the transcobalamin antibodies generated in response to elevated Vitamin B12.