Version 1
: Received: 28 April 2024 / Approved: 29 April 2024 / Online: 29 April 2024 (16:53:57 CEST)
How to cite:
Helgudottir, S. S.; Johnsen, K. B.; Routhe, L. G.; Rasmussen, C. L.; Thomsen, M. S.; Moos, T. Upregulation of Transferrin Receptor 1 (TfR1) at the Blood‐Brain Barrier by Valproic Acid, but Not of Glucose Transporter 1 (GLUT1) or CD98hc. Preprints2024, 2024041939. https://doi.org/10.20944/preprints202404.1939.v1
Helgudottir, S. S.; Johnsen, K. B.; Routhe, L. G.; Rasmussen, C. L.; Thomsen, M. S.; Moos, T. Upregulation of Transferrin Receptor 1 (TfR1) at the Blood‐Brain Barrier by Valproic Acid, but Not of Glucose Transporter 1 (GLUT1) or CD98hc. Preprints 2024, 2024041939. https://doi.org/10.20944/preprints202404.1939.v1
Helgudottir, S. S.; Johnsen, K. B.; Routhe, L. G.; Rasmussen, C. L.; Thomsen, M. S.; Moos, T. Upregulation of Transferrin Receptor 1 (TfR1) at the Blood‐Brain Barrier by Valproic Acid, but Not of Glucose Transporter 1 (GLUT1) or CD98hc. Preprints2024, 2024041939. https://doi.org/10.20944/preprints202404.1939.v1
APA Style
Helgudottir, S. S., Johnsen, K. B., Routhe, L. G., Rasmussen, C. L., Thomsen, M. S., & Moos, T. (2024). Upregulation of Transferrin Receptor 1 (TfR1) at the Blood‐Brain Barrier by Valproic Acid, but Not of Glucose Transporter 1 (GLUT1) or CD98hc. Preprints. https://doi.org/10.20944/preprints202404.1939.v1
Chicago/Turabian Style
Helgudottir, S. S., Maj Schneider Thomsen and Torben Moos. 2024 "Upregulation of Transferrin Receptor 1 (TfR1) at the Blood‐Brain Barrier by Valproic Acid, but Not of Glucose Transporter 1 (GLUT1) or CD98hc" Preprints. https://doi.org/10.20944/preprints202404.1939.v1
Abstract
Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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