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Nutrients
Volume 13
Issue 2
10.3390/nu13020617
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Article

Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine

by
Trevor Teafatiller
1,
Christopher W. Heskett
1,
Anshu Agrawal
1,
Jonathan S. Marchant
2,
Janet E. Baulch
3,
Munjal M. Acharya
3 and
Veedamali S. Subramanian
1,*
1
Department of Medicine, University of California, Irvine, CA 92697, USA
2
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA
3
Department of Radiation Oncology, University of California, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
Nutrients 2021, 13(2), 617; https://doi.org/10.3390/nu13020617
Submission received: 14 December 2020 / Revised: 5 February 2021 / Accepted: 11 February 2021 / Published: 14 February 2021
(This article belongs to the Special Issue The Impact of Micronutrients on the Clinical Condition of Chronic Disease)
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Abstract

The process of obtaining ascorbic acid (AA) via intestinal absorption and blood circulation is carrier-mediated utilizing the AA transporters SVCT1 and SVCT2, which are expressed in the intestine and brain (SVCT2 in abundance). AA concentration is decreased in Alzheimer’s disease (AD), but information regarding the status of intestinal AA uptake in the AD is still lacking. We aimed here to understand how AA homeostasis is modulated in a transgenic mouse model (5xFAD) of AD. AA levels in serum from 5xFAD mice were markedly lower than controls. Expression of oxidative stress response genes (glutathione peroxidase 1 (GPX1) and superoxide dismutase 1 (SOD1)) were significantly increased in AD mice jejunum, and this increase was mitigated by AA supplementation. Uptake of AA in the jejunum was upregulated. This increased AA transport was caused by a marked increase in SVCT1 and SVCT2 protein, mRNA, and heterogeneous nuclear RNA (hnRNA) expression. A significant increase in the expression of HNF1α and specific protein 1 (Sp1), which drive SLC23A1 and SLC23A2 promoter activity, respectively, was observed. Expression of hSVCT interacting proteins GRHPR and CLSTN3 were also increased. SVCT2 protein and mRNA expression in the hippocampus of 5xFAD mice was not altered. Together, these investigations reveal adaptive up-regulation of intestinal AA uptake in the 5xFAD mouse model.
Keywords: Vitamin C; transport; Alzheimer’s disease; SVCT1; SVCT2 Vitamin C; transport; Alzheimer’s disease; SVCT1; SVCT2

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MDPI and ACS Style

Teafatiller, T.; Heskett, C.W.; Agrawal, A.; Marchant, J.S.; Baulch, J.E.; Acharya, M.M.; Subramanian, V.S. Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine. Nutrients 2021, 13, 617. https://doi.org/10.3390/nu13020617

AMA Style

Teafatiller T, Heskett CW, Agrawal A, Marchant JS, Baulch JE, Acharya MM, Subramanian VS. Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine. Nutrients. 2021; 13(2):617. https://doi.org/10.3390/nu13020617

Chicago/Turabian Style

Teafatiller, Trevor, Christopher W. Heskett, Anshu Agrawal, Jonathan S. Marchant, Janet E. Baulch, Munjal M. Acharya, and Veedamali S. Subramanian. 2021. "Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine" Nutrients 13, no. 2: 617. https://doi.org/10.3390/nu13020617

APA Style

Teafatiller, T., Heskett, C. W., Agrawal, A., Marchant, J. S., Baulch, J. E., Acharya, M. M., & Subramanian, V. S. (2021). Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine. Nutrients, 13(2), 617. https://doi.org/10.3390/nu13020617

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