Intracellular and tissue levels of vitamin b12 in hepatocytes are modulated by cd320 receptor and tcn2 transporter
Intracellular and tissue levels of vitamin b12 in hepatocytes are modulated by cd320 receptor and tcn2 transporter
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 de-creased 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.
B12 receptor (CD320), B12 transporter (transcobalamin II, Hepatocytes, Intrinsic factor, TCN2), Vitamin B12 (cobalamin), transcobalamin
Boachie, Joseph
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Adaikalakoteswari, Antonysunil
1640672d-7714-43cf-8a69-d68414bb1e75
Goljan, Ilona
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Samavat, Jinous
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Cagampang, Felino R.
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Saravanan, Ponnusamy
c7907a23-4c95-44f3-9f34-72c779906ea1
17 March 2021
Boachie, Joseph
d42127bb-16e4-4770-93ee-87070887b824
Adaikalakoteswari, Antonysunil
1640672d-7714-43cf-8a69-d68414bb1e75
Goljan, Ilona
6cab36d2-b35a-4cd5-b70d-b12edcd95f09
Samavat, Jinous
f36e792b-07f7-47db-bd7f-a6604d77a098
Cagampang, Felino R.
7cf57d52-4a65-4554-8306-ed65226bc50e
Saravanan, Ponnusamy
c7907a23-4c95-44f3-9f34-72c779906ea1
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).
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 de-creased 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.
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ijms-22-03089-v2
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Accepted/In Press date: 14 March 2021
Published date: 17 March 2021
Keywords:
B12 receptor (CD320), B12 transporter (transcobalamin II, Hepatocytes, Intrinsic factor, TCN2), Vitamin B12 (cobalamin), transcobalamin
Identifiers
Local EPrints ID: 493782
URI: http://eprints.soton.ac.uk/id/eprint/493782
ISSN: 1661-6596
PURE UUID: b0293777-a4a0-43c4-a8ef-438de36536b2
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Date deposited: 12 Sep 2024 16:46
Last modified: 14 Sep 2024 01:39
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Contributors
Author:
Joseph Boachie
Author:
Antonysunil Adaikalakoteswari
Author:
Ilona Goljan
Author:
Jinous Samavat
Author:
Ponnusamy Saravanan
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