PMID- 33672967
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20221207
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 13
IP  - 2
DP  - 2021 Feb 14
TI  - Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse 
      Intestine.
LID - 10.3390/nu13020617 [doi]
LID - 617
AB  - 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 HNF1alpha 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.
FAU - Teafatiller, Trevor
AU  - Teafatiller T
AD  - Department of Medicine, University of California, Irvine, CA 92697, USA.
FAU - Heskett, Christopher W
AU  - Heskett CW
AD  - Department of Medicine, University of California, Irvine, CA 92697, USA.
FAU - Agrawal, Anshu
AU  - Agrawal A
AD  - Department of Medicine, University of California, Irvine, CA 92697, USA.
FAU - Marchant, Jonathan S
AU  - Marchant JS
AD  - Department of Cell Biology, Neurobiology, and Anatomy, Medical College of 
      Wisconsin, Milwaukee, WI 53226, USA.
FAU - Baulch, Janet E
AU  - Baulch JE
AD  - Department of Radiation Oncology, University of California, Irvine, CA 92697, 
      USA.
FAU - Acharya, Munjal M
AU  - Acharya MM
AD  - Department of Radiation Oncology, University of California, Irvine, CA 92697, 
      USA.
FAU - Subramanian, Veedamali S
AU  - Subramanian VS
AD  - Department of Medicine, University of California, Irvine, CA 92697, USA.
LA  - eng
GR  - DK107474/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20210214
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Clstn3 protein, mouse)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Hnf1a protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sodium-Coupled Vitamin C Transporters)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.26 (glyoxylate reductase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - EC 1.11.1.9 (Glutathione Peroxidase GPX1)
RN  - EC 1.11.1.9 (Gpx1 protein, mouse)
SB  - IM
MH  - Alcohol Oxidoreductases/metabolism
MH  - Alzheimer Disease/*metabolism
MH  - Animals
MH  - Ascorbic Acid/*metabolism
MH  - Biological Transport/genetics
MH  - Calcium-Binding Proteins/metabolism
MH  - Dietary Supplements
MH  - Disease Models, Animal
MH  - Glutathione Peroxidase/metabolism
MH  - Hepatocyte Nuclear Factor 1-alpha/metabolism
MH  - Hippocampus/metabolism
MH  - Homeostasis/genetics
MH  - Intestinal Absorption/genetics
MH  - Jejunum/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Oxidative Stress/genetics
MH  - RNA, Messenger/metabolism
MH  - Sodium-Coupled Vitamin C Transporters/*metabolism
MH  - Superoxide Dismutase-1/metabolism
MH  - Up-Regulation/*genetics
MH  - Glutathione Peroxidase GPX1
PMC - PMC7918291
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - SVCT1
OT  - SVCT2
OT  - Vitamin C
OT  - transport
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/03/07 06:00
MHDA- 2021/05/15 06:00
PMCR- 2021/02/14
CRDT- 2021/03/06 01:14
PHST- 2020/12/14 00:00 [received]
PHST- 2021/02/05 00:00 [revised]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/03/06 01:14 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2021/02/14 00:00 [pmc-release]
AID - nu13020617 [pii]
AID - nutrients-13-00617 [pii]
AID - 10.3390/nu13020617 [doi]
PST - epublish
SO  - Nutrients. 2021 Feb 14;13(2):617. doi: 10.3390/nu13020617.