Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment

Kathryn A. Bauerly, Shannon L. Kelleher, Bo Lönnerdal

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Ctr1 and Atp7A are copper (Cu) transporters that may play a role in the regulation of intestinal Cu absorption; however, intestinal regulation of these transporters by Cu in vivo has not been well defined. In this study, we hypothesized that Cu supplementation would alter the expression of intestine Ctr1 and Atp7A in vivo and further documented effects of Cu exposure on Cu transport, Ctr1 and Atp7A levels and localization in enterocyte-like Caco-2 cells. Suckling rat pups were supplemented with Cu (0 and 25 μg Cu/day) for 10 days and small intestine Cu concentration, Ctr1, Atp7A and metallothionein (MT) gene expression were measured by Northern blot analysis. Caco-2 cells were treated with basal medium, or medium supplemented with 3 and 94 μM CuSO 4 and 67Cu transport, Ctr1 and Atp7A levels and localization were determined. In rat pups, Cu supplementation increased intestinal Cu, Ctr1 and MT gene expression; however, Atp7A gene expression was not significantly affected. Caco-2 cells treated with 94 μM Cu had lower cellular Cu uptake and export compared to untreated cells. While Ctr1 and Atp7A gene and protein levels were unaffected, confocal microscopy indicated that Ctr1 was endocytosed and co-localized with transferrin in Cu treated cells. This study demonstrates the functional response of intestinal cells to Cu treatment and suggests that both Ctr1 and Atp7A may regulate Cu absorption.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume15
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Caco-2 Cells
Gene expression
Rats
Copper
Metallothionein
Gene Expression
Enterocytes
Confocal microscopy
Intestinal Absorption
Transferrin
Endocytosis
Confocal Microscopy
Northern Blotting
Small Intestine
Intestines
Cells
Proteins

Keywords

  • Atp7A
  • Caco-2 cells
  • Ctrl
  • Cu, Cu transport
  • Intestine

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment. / Bauerly, Kathryn A.; Kelleher, Shannon L.; Lönnerdal, Bo.

In: Journal of Nutritional Biochemistry, Vol. 15, No. 3, 03.2004, p. 155-162.

Research output: Contribution to journalArticle

Bauerly, Kathryn A. ; Kelleher, Shannon L. ; Lönnerdal, Bo. / Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment. In: Journal of Nutritional Biochemistry. 2004 ; Vol. 15, No. 3. pp. 155-162.
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