Expression of SFT (Stimulator of Fe Transport) Is Enhanced by Iron Chelation in HeLa Cells and by Hemochromatosis in Liver

Yu, Jianming; Yu, Zhong; Wessling‐Resnick, Marianne

doi:10.1074/jbc.273.52.34675

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…The mechanism by which Fe 2ϩ crosses the cell membrane also remains unknown. Although recent studies have identified several molecules mediating Fe 2ϩ uptake, the role of these proteins in iron efflux has not been explored (32)(33)(34)(35).…”

mentioning

confidence: 99%

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

Harris

Durley

Man

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

529

372

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mentioning

confidence: 99%

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

Harris

Durley

Man

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

529

372

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“…Most authors favor the hypothesis that the absence of functional HFE results in an erroneous sensing of body iron stores in immature duodenal crypt cells. [1][2][3][4] In addition, signaling molecules such as the putative iron store regulator hepcidin, 28 or proteins such as SFT, a stimulator of Fe transport, [12][13][14][15] may contribute to the etiology of HH.…”

Section: Discussionmentioning

confidence: 99%

“…12,15,24 Since the UbcH5A 3Ј UTR (GenBank accession no. AJ272367) is almost identical to the previously published SFT 3Ј UTR (GenBank accession no.…”

Section: Ubch5a Transcript Levels Are Not Regulated In Response To Cementioning

confidence: 99%

“…[12][13][14] Accordingly, Northern analysis indicated that SFT expression is up-regulated in iron-deficient HeLa cells exposed to the iron chelator deferoxamine and down-regulated in iron-supplemented HeLa and HepG2 cells. 15 Remarkably, hepatic SFT expression was found to be significantly increased in patients with hereditary hemochromatosis (HH) despite tissue iron overload. 15 In most cases, this frequent autosomal recessive disorder is associated with a missense mutation (Cys282Tyr) in the hemochromatosis gene HFE, which codes for a protein that is homologous to class I major histocompatibility complex (MHC) molecules and requires ␤2-microglobulin (light chain) for surface presentation.…”

Section: Introductionmentioning

confidence: 99%

“…15 Remarkably, hepatic SFT expression was found to be significantly increased in patients with hereditary hemochromatosis (HH) despite tissue iron overload. 15 In most cases, this frequent autosomal recessive disorder is associated with a missense mutation (Cys282Tyr) in the hemochromatosis gene HFE, which codes for a protein that is homologous to class I major histocompatibility complex (MHC) molecules and requires ␤2-microglobulin (light chain) for surface presentation. [16][17][18] However, there is still some evidence that other genetic factors influence expression of the disease.…”

Section: Introductionmentioning

confidence: 99%

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UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis

Gehrke

Riedel

Herrmann

et al. 2003

Blood

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SFT, a stimulator of iron (Fe) transport, has been described as a transmembrane protein that facilitates the uptake of ferrous and ferric iron in mammalian cells. This study was initiated to investigate the 5 regulatory region of SFT and its role in the etiology of hereditary hemochromatosis. Sequence analyses of the putative 5 regulatory region revealed that the SFT cDNA sequence corresponds to intron 6/exon 7 of UbcH5A, a member of E2 ubiquitin-conjugating enzymes, which is involved in the iron-dependent ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. Further mRNA expression studies using a sequence-specific reverse transcriptasepolymerase chain reaction (RT-PCR) assay showed that UbcH5A is significantly upregulated in the liver of iron-overloaded patients with hereditary hemochromatosis, as previously published for SFT. However, in vitro studies on HepG2 cells failed to demonstrate any significant UbcH5A regulation in response to iron loading or iron chelation. In conclusion, in vivo mRNA expression data previously obtained for SFT might be attributed to UbcH5A.

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Iron absorption and transport?An update

2000

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Iron is vital for all living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where heme is a significant part of the diet, most body iron is derived from dietary heme iron because heme binds few of the luminal intestinal iron chelators that inhibit absorption of non-heme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intra-cellularly, iron is released from heme by heme oxygenase so that iron leaves the entero-cyte to enter the plasma as non-heme iron. Ferric iron is absorbed via a 3 integrin and mobilferrin (IMP) pathway that is not shared with other nutritional metals. Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese. Other proteins were recently described which are believed to play a role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from entero-cytes into the plasma. The iron concentration within enterocytes reflects the total body iron and either upregulates or satiates iron-binding sites on regulatory proteins. Entero-cytes of hemochromatotics are iron-depleted similarly to the absorptive cells of iron-deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorption. In non-intestinal cells most iron uptake occurs via either the classical clathrin-coated pathway utilizing transferrin receptors or the poorly defined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overload is unclear. This suggests that these pathways have intracellular functions in addition to facilitating iron uptake. Am. J. Hematol. 64:287-298, 2000.

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Expression of SFT (Stimulator of Fe Transport) Is Enhanced by Iron Chelation in HeLa Cells and by Hemochromatosis in Liver

Cited by 25 publications

References 34 publications

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis

Iron absorption and transport?An update

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