PMID- 18419598 OWN - NLM STAT- MEDLINE DCOM- 20080908 LR - 20211020 IS - 1582-1838 (Print) IS - 1582-4934 (Electronic) IS - 1582-1838 (Linking) VI - 12 IP - 2 DP - 2008 Apr TI - Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells. PG - 569-79 LID - 10.1111/j.1582-4934.2007.00145.x [doi] AB - 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. FAU - Li, Zhu AU - Li Z AD - Institute for Nautical Medicine and Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, PR China. FAU - Lai, Zhang AU - Lai Z FAU - Ya, Ke AU - Ya K FAU - Fang, Du AU - Fang D FAU - Ho, Yung Wing AU - Ho YW FAU - Lei, Yang AU - Lei Y FAU - Ming, Qian Zhong AU - Ming QZ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Cation Transport Proteins) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Iron-Regulatory Proteins) RN - 0 (Protein Isoforms) RN - 0 (solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2) RN - 3G0H8C9362 (Cobalt) RN - EVS87XF13W (cobaltous chloride) SB - IM MH - Carcinoma, Hepatocellular/*metabolism/pathology MH - Cation Transport Proteins/genetics/*metabolism MH - Cell Hypoxia MH - Cell Line, Tumor MH - Cell Nucleus/metabolism MH - Cell Survival/drug effects MH - Cobalt/pharmacology MH - Cytoplasm/metabolism MH - Dose-Response Relationship, Drug MH - Humans MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - Immunohistochemistry MH - Iron-Regulatory Proteins/genetics/*metabolism MH - Liver Neoplasms/*metabolism/pathology MH - Protein Isoforms/genetics/metabolism MH - Time Factors PMC - PMC3822544 EDAT- 2008/04/19 09:00 MHDA- 2008/09/09 09:00 PMCR- 2008/04/01 CRDT- 2008/04/19 09:00 PHST- 2008/04/19 09:00 [pubmed] PHST- 2008/09/09 09:00 [medline] PHST- 2008/04/19 09:00 [entrez] PHST- 2008/04/01 00:00 [pmc-release] AID - JCMM145 [pii] AID - 10.1111/j.1582-4934.2007.00145.x [doi] PST - ppublish SO - J Cell Mol Med. 2008 Apr;12(2):569-79. doi: 10.1111/j.1582-4934.2007.00145.x.