ArticleProceedings of the National Academy of Sciences of the United States of America2009
Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 80 citations in OpenAlex.
- Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7.Haematologica · 2011Trial
- SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism.Cell reports. Medicine · 2026Article
- CD320 Receptor and Vitamin B12 as Potential Targets for Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review.Journal of endocrinological investigation · 2025Article
- A systematic approach towards long-term, serum-free cultivation of fish cells with the RTgill-W1 cell line as example.NAM journal · 2025Article
- Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.International journal of molecular sciences · 2024Review
- Folate and Cobalamin Deficiencies during Pregnancy Disrupt the Glucocorticoid Response in Hypothalamus throughInternational journal of molecular sciences · 2023Article
- Altered vitamin B12 metabolism in the central nervous system is associated with the modification of ribosomal gene expression: new insights from comparative RNA dataset analysis.Functional & integrative genomics · 2023Article
- Article
- The opportunities and challenges for nutritional intervention in childhood cancers.Frontiers in nutrition · 2023Review
- The relationship between nutrition and the immune system.Frontiers in nutrition · 2022Review
- Glucocorticoid Receptor Activation Restores Learning Memory by Modulating Hippocampal Plasticity in a Mouse Model of Brain Vitamin BMolecular neurobiology · 2021Article
- Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist.Biology · 2021Article
- Antivitamins BChemistry (Weinheim an der Bergstrasse, Germany) · 2020Review
- Article
- The Stimulation of Neurogenesis Improves the Cognitive Status of Aging Rats Subjected to Gestational and Perinatal Deficiency of B9-12 Vitamins.International journal of molecular sciences · 2020Article
- Valproic acid upregulates the expression of the p75NTR/sortilin receptor complex to induce neuronal apoptosis.Apoptosis : an international journal on programmed cell death · 2020Article
- Review
- Brain Susceptibility to Methyl Donor Deficiency: From Fetal Programming to Aging Outcome in Rats.International journal of molecular sciences · 2019Article
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin B12 (cobalamin, Cbl) is indispensable for proper brain development and functioning, suggesting that it has neurotrophic effects beside its well-known importance in metabolism. The molecular basis of these effects remains hypothetical, one of the reasons being that no efficient cell model has been made available for investigating the consequences of B12 cellular deficiency in neuronal cells. Here, we designed an approach by stable transfection of NIE115 neuroblastoma cells to impose the anchorage of a chimeric B12-binding protein, transcobalamin-oleosin (TO) to the intracellular membrane. This model produced an intracellular sequestration of B12 evidenced by decreased methyl-Cbl and S-adenosylmethionine and increased homocysteine and methylmalonic acid concentrations. B12 deficiency affected the proliferation of NIE115 cells through an overall increase in catalytic protein phosphatase 2A (PP2A), despite its demethylation. It promoted cellular differentiation by improving initial outgrowth of neurites and, at the molecular level, by augmenting the levels of proNGF and p75(NTR). The up-regulation of PP2A and pro-nerve growth factor (NGF) triggered changes in ERK1/2 and Akt, two signaling pathways that influence the balance between proliferation and neurite outgrowth. Compared with control cells, a 2-fold increase of p75(NTR)-regulated intramembraneous proteolysis (RIP) was observed in proliferating TO cells (P < 0.0001) that was associated with an increased expression of two tumor necrosis factor (TNF)-alpha converting enzyme (TACE) secretase enzymes, Adam 10 and Adam 17. In conclusion, our data show that B12 cellular deficiency produces a slower proliferation and a speedier differentiation of neuroblastoma cells through interacting signaling pathways that are related with increased expression of PP2A, proNGF, and TACE.
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