Function and Regulation of Intestinal Zinc Transporter ZIP14

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Material Information

Title:
Function and Regulation of Intestinal Zinc Transporter ZIP14
Physical Description:
1 online resource (113 p.)
Language:
english
Creator:
Guthrie, Gregory J
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Nutritional Sciences
Committee Chair:
COUSINS,ROBERT J
Committee Co-Chair:
HENKEN,ROBIN J
Committee Members:
COLLINS,JAMES FORREST
ANTON,STEPHEN D

Subjects

Subjects / Keywords:
claudin1 -- intestine -- lps -- occludin -- permeability -- slc39a14 -- zinc -- zip14
Nutritional Sciences -- Dissertations, Academic -- UF
Genre:
Nutritional Sciences thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
ZIP14 is a transporter that increases the intracellular labile pool of zinc.   ZIP14 has a high level of expression in the gastrointestinal (gi) tract, yet loss ofthe gene is not embryonically lethal, suggesting Zip14 may function in specialized zinc transport in the intestine. ZIP14 is responsive to endotoxin-induced inflammation and intestinal permeability increases in response to inflammation.  Zinc supplementation decreases intestinal permeability, but whether that effect is dependent upon a zinc transporter is unknown.  Based on these observations the hypothesis of this research is that ZIP14 is a zinc transporter that is responsible for zinc homeostasis in both basal and inflammation-mediated conditions which helps maintain intestinal function.  In vivo experiments were performed with wild type (Zip14+/+)mice or a knockout mouse model of Zip14 (Zip14-/-).  Western blots of extracts from isolated intestinal segments show ZIP14 protein distribution highest along the duodenum and decreases towards the colon.  Isolated intestinal cytoplasmic and membrane fractions were used to determine ZIP14 is localized to the basolateral membrane. Intestinal uptake studies using 65Zn administered orally bygavage or subcutaneously (sc) were performed. 65Zn was higher in the Zip14-/-compared to Zip14+/+genotype in G.I. tissue, following sc injections, but not oral gavage.  To determine an effect of endotoxin on intestinal ZIP14, LPS was injected intraperitoneally.  ZIP14 transcript levels did not change within 18 hr, after the LPS, but protein levels decreased at 3- and 6-hr.  This response is opposite to results observed in liver ZIP14.  Additionally, 65Zn studies with sc injection and oral gavage showed no difference in zinc transport between Zip14+/+and Zip14-/- in response to LPS.  Lastly, Zip14-/- mice following an oral gavage of FITC-dextran,a fluorescent permeability marker, have higher plasma FITC-dextran compared to Zip14+/+ mice.  This increased intestinal permeability coincides with decreased expression of the tight junction proteins claudin-1 and occludin in the Zip14-/-mice.  Furthermore, threonine phosphorylation of occludin, which is necessary for tight junction assembly, is decreased in Zip14-/-mice.  In conclusion, ZIP14 is a basolateral zinc transporter that does not increase expression in response to LPS, but is necessary for the maintenance of intestinal barrier function.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Gregory J Guthrie.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: COUSINS,ROBERT J.
Local:
Co-adviser: HENKEN,ROBIN J.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-12-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0046238:00001