Boachie, Joseph, Adaikalakoteswari, Antonysunil, Goljan, Ilona, Samavat, Jinous, Cagampang, Felino R. and Saravanan, Ponnusamy (2021) Intracellular and tissue levels of vitamin B12 in hepatocytes are modulated by CD320 receptor and TCN2 transporter. International Journal of Molecular Sciences, 22 (6). 3089. doi:10.3390/ijms22063089 ISSN 1422-0067.
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Abstract
The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immunoassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 µg B12/kg and 7.49 µg B12/kg, respectively) for 8-10 weeks. The physiological B12 status (0.15-1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (>1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extracellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
| SWORD Depositor: | Library Publications Router |
| Library of Congress Subject Headings (LCSH): | Vitamin B12 , Vitamin B12 -- Receptors, Liver cells , Cell membranes , Cell receptors |
| Journal or Publication Title: | International Journal of Molecular Sciences |
| Publisher: | M D P I AG |
| ISSN: | 1422-0067 |
| Official Date: | 17 March 2021 |
| Dates: | Date Event 17 March 2021 Published 14 March 2021 Accepted |
| Volume: | 22 |
| Number: | 6 |
| Article Number: | 3089 |
| DOI: | 10.3390/ijms22063089 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Open Access (Creative Commons open licence) |
| Date of first compliant deposit: | 11 June 2021 |
| Date of first compliant Open Access: | 11 June 2021 |
| RIOXX Funder/Project Grant: | Project/Grant ID RIOXX Funder Name Funder ID |
| URI: | https://wrap.warwick.ac.uk/151271/ |
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