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Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption

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Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin : A role for PI3K in intestinal iron absorption. / Kondaiah, Palsa; Sharp, Paul A.; Pullakhandam, Raghu.

In: Biochemical and Biophysical Research Communications, Vol. 523, No. 4, 19.03.2020, p. 987-992.

Research output: Contribution to journalArticle

Harvard

Kondaiah, P, Sharp, PA & Pullakhandam, R 2020, 'Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption', Biochemical and Biophysical Research Communications, vol. 523, no. 4, pp. 987-992. https://doi.org/10.1016/j.bbrc.2020.01.023

APA

Kondaiah, P., Sharp, P. A., & Pullakhandam, R. (2020). Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption. Biochemical and Biophysical Research Communications, 523(4), 987-992. https://doi.org/10.1016/j.bbrc.2020.01.023

Vancouver

Kondaiah P, Sharp PA, Pullakhandam R. Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption. Biochemical and Biophysical Research Communications. 2020 Mar 19;523(4):987-992. https://doi.org/10.1016/j.bbrc.2020.01.023

Author

Kondaiah, Palsa ; Sharp, Paul A. ; Pullakhandam, Raghu. / Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin : A role for PI3K in intestinal iron absorption. In: Biochemical and Biophysical Research Communications. 2020 ; Vol. 523, No. 4. pp. 987-992.

Bibtex Download

@article{87cee36a0c2f4305893f74e6dde2c7e6,
title = "Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption",
abstract = "In previous studies we demonstrated that zinc stimulates iron uptake in intestinal Caco-2 cells via Zinc-PI3K-IRP2-DMT1 axis. In the current study we investigated the effect of zinc on basolateral iron release and characterized the associated mechanisms. In Caco-2 cells grown on permeable supports, zinc induced iron transport and expression of DMT1, HEPH mRNA and protein, but not that of FPN1. LY294002, an inhibitor of PI3K, inhibited the zinc-induced iron transport, DMT1, HEPH mRNA and protein expression. In addition, LY294002 also inhibited the basal expression of HEPH and FPN1 resulting in blockade of iron egress from cells. In addition, siRNA-silencing of HEPH led to inhibition of both zinc-induced and basal iron transport. Conversely, TPEN, a chelator of zinc, inhibited iron uptake, DMT1, HEPH and FPN1 mRNA and protein expression. These results suggest that intestinal cell zinc status is a critical determinant of iron absorption and effects are mediated via activation of PI3K. Further, PI3K pathway appears to selectively modulate the expression of iron transporters and iron absorption, therefore this might serve as a therapeutic target in iron overload disorders.",
keywords = "Caco-2 cells, Hephaestin, Interactions, Iron, Iron transporters, PI3K, siRNA, Zinc",
author = "Palsa Kondaiah and Sharp, {Paul A.} and Raghu Pullakhandam",
year = "2020",
month = mar,
day = "19",
doi = "10.1016/j.bbrc.2020.01.023",
language = "English",
volume = "523",
pages = "987--992",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "ACADEMIC PRESS INC",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin

T2 - A role for PI3K in intestinal iron absorption

AU - Kondaiah, Palsa

AU - Sharp, Paul A.

AU - Pullakhandam, Raghu

PY - 2020/3/19

Y1 - 2020/3/19

N2 - In previous studies we demonstrated that zinc stimulates iron uptake in intestinal Caco-2 cells via Zinc-PI3K-IRP2-DMT1 axis. In the current study we investigated the effect of zinc on basolateral iron release and characterized the associated mechanisms. In Caco-2 cells grown on permeable supports, zinc induced iron transport and expression of DMT1, HEPH mRNA and protein, but not that of FPN1. LY294002, an inhibitor of PI3K, inhibited the zinc-induced iron transport, DMT1, HEPH mRNA and protein expression. In addition, LY294002 also inhibited the basal expression of HEPH and FPN1 resulting in blockade of iron egress from cells. In addition, siRNA-silencing of HEPH led to inhibition of both zinc-induced and basal iron transport. Conversely, TPEN, a chelator of zinc, inhibited iron uptake, DMT1, HEPH and FPN1 mRNA and protein expression. These results suggest that intestinal cell zinc status is a critical determinant of iron absorption and effects are mediated via activation of PI3K. Further, PI3K pathway appears to selectively modulate the expression of iron transporters and iron absorption, therefore this might serve as a therapeutic target in iron overload disorders.

AB - In previous studies we demonstrated that zinc stimulates iron uptake in intestinal Caco-2 cells via Zinc-PI3K-IRP2-DMT1 axis. In the current study we investigated the effect of zinc on basolateral iron release and characterized the associated mechanisms. In Caco-2 cells grown on permeable supports, zinc induced iron transport and expression of DMT1, HEPH mRNA and protein, but not that of FPN1. LY294002, an inhibitor of PI3K, inhibited the zinc-induced iron transport, DMT1, HEPH mRNA and protein expression. In addition, LY294002 also inhibited the basal expression of HEPH and FPN1 resulting in blockade of iron egress from cells. In addition, siRNA-silencing of HEPH led to inhibition of both zinc-induced and basal iron transport. Conversely, TPEN, a chelator of zinc, inhibited iron uptake, DMT1, HEPH and FPN1 mRNA and protein expression. These results suggest that intestinal cell zinc status is a critical determinant of iron absorption and effects are mediated via activation of PI3K. Further, PI3K pathway appears to selectively modulate the expression of iron transporters and iron absorption, therefore this might serve as a therapeutic target in iron overload disorders.

KW - Caco-2 cells

KW - Hephaestin

KW - Interactions

KW - Iron

KW - Iron transporters

KW - PI3K

KW - siRNA

KW - Zinc

UR - http://www.scopus.com/inward/record.url?scp=85078067608&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2020.01.023

DO - 10.1016/j.bbrc.2020.01.023

M3 - Article

AN - SCOPUS:85078067608

VL - 523

SP - 987

EP - 992

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -

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