Effects of zinc exposure on zinc transporter expression in human intestinal cells of varying maturity

Ming Yu Jou, Anthony F Philipps, Shannon L. Kelleher, Bo Lönnerdal

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

OBJECTIVES: Zinc (Zn) homeostasis in adults is achieved principally through a balance between intestinal absorption and excretion involving adaptive mechanisms programmed by levels of dietary Zn. Zn absorption in infants is not as tightly regulated as that in adults, which may induce potential toxicity in infants due to the relatively high capacity of Zn absorption. We hypothesized that intestinal Zn homeostasis is developmentally regulated and depends on intestinal maturation, which in turn affects Zn transporter regulation. MATERIALS AND METHODS: Cultured human fetal (FHs 74 Int, F) and adult (Caco-2: undifferentiated, U; differentiated, D) intestinal cells were used to determine developmental differences in Zn uptake and effects of Zn exposure on Zn transporters. RESULTS: Zn uptake rates in F and U cells were higher compared with D cells (F, 9-fold; U, 3-fold). F cells were more intolerant to Zn exposure than were U or D cells (LD50 = 67.9 ± 5.3; 117.0 ± 5.2; 224.4 ± 3.7 μmol/L, respectively). Two mechanisms were involved in developmental regulation of Zn homeostasis: differential Zn transporter expression and differential response to Zn exposure. In F cells, zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT)-like protein (Zip)4 expression was undetectable; Zn (50 μmol/L) increased levels of Zn transporter (ZnT)1, ZnT2, and metallothionein-1 mRNA and ZnT1 protein. U and D cells had higher mRNA expression of ZnT1 (U: 5-fold; D: 7-fold, respectively) and ZnT2 (U: 2-fold; D: 9-fold, respectively) than F cells, and D cells also had higher Zip4 expression (3-fold) than U cells. In U cells, Zn exposure increased Zip4 protein level, but not membrane-associated abundance. However, in D cells, Zn exposure decreased both the Zip4 protein level and membrane-associated abundance. CONCLUSIONS: Zn absorption is developmentally regulated through intestinal Zn efflux and sequestration and import mechanisms, which may be responsible for differences in Zn absorption observed between infants and adults.

Original languageEnglish (US)
Pages (from-to)587-595
Number of pages9
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume50
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Zinc
Somatostatin-Secreting Cells
zinc-binding protein
Homeostasis
Messenger RNA
Proteins
Metallothionein
Lethal Dose 50
Intestinal Absorption
Membrane Proteins
Iron

Keywords

  • Intestinal maturation
  • Zinc absorption
  • Zinc homeostasis
  • Zinc transporters

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

Cite this

Effects of zinc exposure on zinc transporter expression in human intestinal cells of varying maturity. / Jou, Ming Yu; Philipps, Anthony F; Kelleher, Shannon L.; Lönnerdal, Bo.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 50, No. 6, 06.2010, p. 587-595.

Research output: Contribution to journalArticle

@article{4973eca7e6ea46278f7ed04996515498,
title = "Effects of zinc exposure on zinc transporter expression in human intestinal cells of varying maturity",
abstract = "OBJECTIVES: Zinc (Zn) homeostasis in adults is achieved principally through a balance between intestinal absorption and excretion involving adaptive mechanisms programmed by levels of dietary Zn. Zn absorption in infants is not as tightly regulated as that in adults, which may induce potential toxicity in infants due to the relatively high capacity of Zn absorption. We hypothesized that intestinal Zn homeostasis is developmentally regulated and depends on intestinal maturation, which in turn affects Zn transporter regulation. MATERIALS AND METHODS: Cultured human fetal (FHs 74 Int, F) and adult (Caco-2: undifferentiated, U; differentiated, D) intestinal cells were used to determine developmental differences in Zn uptake and effects of Zn exposure on Zn transporters. RESULTS: Zn uptake rates in F and U cells were higher compared with D cells (F, 9-fold; U, 3-fold). F cells were more intolerant to Zn exposure than were U or D cells (LD50 = 67.9 ± 5.3; 117.0 ± 5.2; 224.4 ± 3.7 μmol/L, respectively). Two mechanisms were involved in developmental regulation of Zn homeostasis: differential Zn transporter expression and differential response to Zn exposure. In F cells, zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT)-like protein (Zip)4 expression was undetectable; Zn (50 μmol/L) increased levels of Zn transporter (ZnT)1, ZnT2, and metallothionein-1 mRNA and ZnT1 protein. U and D cells had higher mRNA expression of ZnT1 (U: 5-fold; D: 7-fold, respectively) and ZnT2 (U: 2-fold; D: 9-fold, respectively) than F cells, and D cells also had higher Zip4 expression (3-fold) than U cells. In U cells, Zn exposure increased Zip4 protein level, but not membrane-associated abundance. However, in D cells, Zn exposure decreased both the Zip4 protein level and membrane-associated abundance. CONCLUSIONS: Zn absorption is developmentally regulated through intestinal Zn efflux and sequestration and import mechanisms, which may be responsible for differences in Zn absorption observed between infants and adults.",
keywords = "Intestinal maturation, Zinc absorption, Zinc homeostasis, Zinc transporters",
author = "Jou, {Ming Yu} and Philipps, {Anthony F} and Kelleher, {Shannon L.} and Bo L{\"o}nnerdal",
year = "2010",
month = "6",
doi = "10.1097/MPG.0b013e3181d98e85",
language = "English (US)",
volume = "50",
pages = "587--595",
journal = "Journal of Pediatric Gastroenterology and Nutrition",
issn = "0277-2116",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Effects of zinc exposure on zinc transporter expression in human intestinal cells of varying maturity

AU - Jou, Ming Yu

AU - Philipps, Anthony F

AU - Kelleher, Shannon L.

AU - Lönnerdal, Bo

PY - 2010/6

Y1 - 2010/6

N2 - OBJECTIVES: Zinc (Zn) homeostasis in adults is achieved principally through a balance between intestinal absorption and excretion involving adaptive mechanisms programmed by levels of dietary Zn. Zn absorption in infants is not as tightly regulated as that in adults, which may induce potential toxicity in infants due to the relatively high capacity of Zn absorption. We hypothesized that intestinal Zn homeostasis is developmentally regulated and depends on intestinal maturation, which in turn affects Zn transporter regulation. MATERIALS AND METHODS: Cultured human fetal (FHs 74 Int, F) and adult (Caco-2: undifferentiated, U; differentiated, D) intestinal cells were used to determine developmental differences in Zn uptake and effects of Zn exposure on Zn transporters. RESULTS: Zn uptake rates in F and U cells were higher compared with D cells (F, 9-fold; U, 3-fold). F cells were more intolerant to Zn exposure than were U or D cells (LD50 = 67.9 ± 5.3; 117.0 ± 5.2; 224.4 ± 3.7 μmol/L, respectively). Two mechanisms were involved in developmental regulation of Zn homeostasis: differential Zn transporter expression and differential response to Zn exposure. In F cells, zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT)-like protein (Zip)4 expression was undetectable; Zn (50 μmol/L) increased levels of Zn transporter (ZnT)1, ZnT2, and metallothionein-1 mRNA and ZnT1 protein. U and D cells had higher mRNA expression of ZnT1 (U: 5-fold; D: 7-fold, respectively) and ZnT2 (U: 2-fold; D: 9-fold, respectively) than F cells, and D cells also had higher Zip4 expression (3-fold) than U cells. In U cells, Zn exposure increased Zip4 protein level, but not membrane-associated abundance. However, in D cells, Zn exposure decreased both the Zip4 protein level and membrane-associated abundance. CONCLUSIONS: Zn absorption is developmentally regulated through intestinal Zn efflux and sequestration and import mechanisms, which may be responsible for differences in Zn absorption observed between infants and adults.

AB - OBJECTIVES: Zinc (Zn) homeostasis in adults is achieved principally through a balance between intestinal absorption and excretion involving adaptive mechanisms programmed by levels of dietary Zn. Zn absorption in infants is not as tightly regulated as that in adults, which may induce potential toxicity in infants due to the relatively high capacity of Zn absorption. We hypothesized that intestinal Zn homeostasis is developmentally regulated and depends on intestinal maturation, which in turn affects Zn transporter regulation. MATERIALS AND METHODS: Cultured human fetal (FHs 74 Int, F) and adult (Caco-2: undifferentiated, U; differentiated, D) intestinal cells were used to determine developmental differences in Zn uptake and effects of Zn exposure on Zn transporters. RESULTS: Zn uptake rates in F and U cells were higher compared with D cells (F, 9-fold; U, 3-fold). F cells were more intolerant to Zn exposure than were U or D cells (LD50 = 67.9 ± 5.3; 117.0 ± 5.2; 224.4 ± 3.7 μmol/L, respectively). Two mechanisms were involved in developmental regulation of Zn homeostasis: differential Zn transporter expression and differential response to Zn exposure. In F cells, zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT)-like protein (Zip)4 expression was undetectable; Zn (50 μmol/L) increased levels of Zn transporter (ZnT)1, ZnT2, and metallothionein-1 mRNA and ZnT1 protein. U and D cells had higher mRNA expression of ZnT1 (U: 5-fold; D: 7-fold, respectively) and ZnT2 (U: 2-fold; D: 9-fold, respectively) than F cells, and D cells also had higher Zip4 expression (3-fold) than U cells. In U cells, Zn exposure increased Zip4 protein level, but not membrane-associated abundance. However, in D cells, Zn exposure decreased both the Zip4 protein level and membrane-associated abundance. CONCLUSIONS: Zn absorption is developmentally regulated through intestinal Zn efflux and sequestration and import mechanisms, which may be responsible for differences in Zn absorption observed between infants and adults.

KW - Intestinal maturation

KW - Zinc absorption

KW - Zinc homeostasis

KW - Zinc transporters

UR - http://www.scopus.com/inward/record.url?scp=77953139645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953139645&partnerID=8YFLogxK

U2 - 10.1097/MPG.0b013e3181d98e85

DO - 10.1097/MPG.0b013e3181d98e85

M3 - Article

C2 - 20479680

AN - SCOPUS:77953139645

VL - 50

SP - 587

EP - 595

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

SN - 0277-2116

IS - 6

ER -