Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells

Donatella Barisani, Gaetano Cairo, Enrico Ginelli, Anna Marozzi, Dario Conte

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) modulate iron regulatory protein (IRP) activity and may, therefore, affect iron uptake through transferrin receptor expression. However, iron also enters the cell as nontransferrin-bound iron (NTBI), and the aim of this study was to evaluate the effects of NO donors on NTBI transport in HepG2 cells, a model of liver physiology. Incubation with SNP and SNAP led to a time- and concentration-dependent reduction in Fe3+ and Fe2+ uptake, thus indicating an effect on the transporter rather than on the reductase. In terms of Fe2+ uptake, no variations in the Michaelis- Menten constant (K(m)) and a reduction in maximum uptake (V(max)) (50, 33, and 16.6 fmol/μg protein/min in control, SNP-, and SNAP-treated cells, respectively) were detected, which suggested a decrease in the number of putative NTBI transport protein(s). Gel shift assays showed that IRP activity was reduced by SNP and slightly increased by SNAP. Northern blot analysis of transferrin receptor messenger RNA (mRNA) levels showed variations similar to those observed for IRPs, but both NO donors increased L-ferritin mRNA levels and had no effect on the stimulator of Fe transport (SFT) mRNA. In conclusion, NO donors significantly reduce NTBI transport in HepG2 cells, an effect that seems to be IRP and SFT independent. Moreover, the reduction in NTBI uptake after NO treatment suggests that this form of iron may play a minor role in the increased hepatic iron stores observed in inflammation or that other liver cells are more involved in this pathological condition.

Original languageEnglish
Pages (from-to)464-470
Number of pages7
JournalHepatology
Volume29
Issue number2
DOIs
Publication statusPublished - 1999

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Hep G2 Cells
Nitric Oxide
Iron
S-Nitroso-N-Acetylpenicillamine
Nitric Oxide Donors
Iron-Regulatory Proteins
Nitroprusside
Transferrin Receptors
Messenger RNA
Liver
Apoferritins
Northern Blotting
Carrier Proteins
Oxidoreductases
Gels
Inflammation

ASJC Scopus subject areas

  • Hepatology

Cite this

Barisani, D., Cairo, G., Ginelli, E., Marozzi, A., & Conte, D. (1999). Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells. Hepatology, 29(2), 464-470. https://doi.org/10.1002/hep.510290205

Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells. / Barisani, Donatella; Cairo, Gaetano; Ginelli, Enrico; Marozzi, Anna; Conte, Dario.

In: Hepatology, Vol. 29, No. 2, 1999, p. 464-470.

Research output: Contribution to journalArticle

Barisani, D, Cairo, G, Ginelli, E, Marozzi, A & Conte, D 1999, 'Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells', Hepatology, vol. 29, no. 2, pp. 464-470. https://doi.org/10.1002/hep.510290205
Barisani, Donatella ; Cairo, Gaetano ; Ginelli, Enrico ; Marozzi, Anna ; Conte, Dario. / Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells. In: Hepatology. 1999 ; Vol. 29, No. 2. pp. 464-470.
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