Intracellular and tissue levels of vitamin B12 in hepatocytes are modulated by CD320 receptor and TCN2 transporter

Boachie, J., Adaikalakoteswari, A. ORCID: 0000-0003-2974-3388, Goljan, I., Samavat, J., Cagampang, F.R. and Saravanan, P., 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. ISSN 1661-6596

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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 immu-noassays, 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 extra-cellular 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
Publication Title: International Journal of Molecular Sciences
Creators: Boachie, J., Adaikalakoteswari, A., Goljan, I., Samavat, J., Cagampang, F.R. and Saravanan, P.
Publisher: MDPI
Date: 2021
Volume: 22
Number: 6
ISSN: 1661-6596
Identifiers:
NumberType
10.3390/ijms22063089DOI
1426398Other
Rights: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 24 Mar 2021 09:34
Last Modified: 24 Mar 2021 09:38
URI: http://irep.ntu.ac.uk/id/eprint/42567

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