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PMID:18419598

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Citation

Li, Z, Lai, Z, Ya, K, Fang, D, Ho, YW, Lei, Y and Ming, QZ (2008) Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells. J. Cell. Mol. Med. 12:569-79

Abstract

Transferrin and transferrin receptor are two key proteins of iron metabolism that have been identified to be hypoxia-inducible genes. Divalent metal transporter 1 (DMT1) is also a key transporter of iron under physiological conditions. In addition, in the 5' regulatory region of human DMT1 (between -412 and -570), there are two motifs (CCAAAGTGCTGGG) that are similar to hypoxia-inducible factor-1 (HIF-1) binding sites. It was therefore speculated that DMT1 might also be a hypoxia-inducible gene. We investigated the effects of hypoxia and hypoxia/re-oxygenation on the expression of DMT1 and the content of HIF-1alpha in HepG2 cells. As we expected, a very similar tendency in the responses of the expression of HIF-1alpha, DMT1+IRE (iron response element) and DMT1-IRE proteins to chemical (CoCl(2)) or physical hypoxia was observed. A highly significant correlation was found between the expression of DMT1 proteins and the contents of HIF-1 in hypoxic cells. After the cells were exposed to hypoxia and subsequent normoxia, no HIF-1alpha could be detected and a significant decrease in DMT1+IRE expression (P<0.05), but not in DMT1-IRE protein (versus the hypoxia group), was observed. The findings implied that the HIF-1 pathway might have a role in the regulation of DMT1+IRE expression during hypoxia.

Links

PubMed Online version:10.1111/j.1582-4934.2007.00145.x

Keywords

Carcinoma, Hepatocellular/metabolism; Carcinoma, Hepatocellular/pathology; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Cell Hypoxia; Cell Line, Tumor; Cell Nucleus/metabolism; Cell Survival/drug effects; Cobalt/pharmacology; Cytoplasm/metabolism; Dose-Response Relationship, Drug; Humans; Hypoxia-Inducible Factor 1/genetics; Hypoxia-Inducible Factor 1/metabolism; Immunohistochemistry; Iron-Regulatory Proteins/genetics; Iron-Regulatory Proteins/metabolism; Liver Neoplasms/metabolism; Liver Neoplasms/pathology; Protein Isoforms/genetics; Protein Isoforms/metabolism; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NRAM2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NRAM2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NRAM2

GO:0001666: response to hypoxia

ECO:0000270:

P

for both P49281-1 and P49281-2 isoforms

complete

HUMAN:NRAM2

GO:0003032: detection of oxygen

ECO:0000270:

P

Positive for P49281-1 and a NOT annotation for P49281-2

complete

HUMAN:NRAM2

GO:0005634: nucleus

ECO:0000314:

C

complete

HUMAN:NRAM2

GO:0005737: cytoplasm

ECO:0000314:

C

complete

HUMAN:NRAM2

NOT|involved_in

GO:0003032: detection of oxygen

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NRAM2

involved_in

GO:0001666: response to hypoxia

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NRAM2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NRAM2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NRAM2

involved_in

GO:0003032: detection of oxygen

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

NOT|involved_in

GO:0003032: detection of oxygen

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Q8IUD7

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Q8IUD7

involved_in

GO:0003032: detection of oxygen

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

involved_in

GO:0001666: response to hypoxia

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HIF1A

involved_in

GO:0010468: regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HIF1A

involved_in

GO:0001666: response to hypoxia

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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