PMID- 19828835
OWN - NLM
STAT- MEDLINE
DCOM- 20091229
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 297
IP  - 6
DP  - 2009 Dec
TI  - The role of transferrin receptor 1 and 2 in transferrin-bound iron uptake in 
      human hepatoma cells.
PG  - C1567-75
LID - 10.1152/ajpcell.00649.2008 [doi]
AB  - Transferrin receptor (TFR) 1 and 2 are expressed in the liver; TFR1 levels are 
      regulated by cellular iron levels while TFR2 levels are regulated by transferrin 
      saturation. The aims of this study were to 1) determine the relative importance 
      of TFR1 and TFR2 in transferrin-bound iron (TBI) uptake by HuH7 human hepatoma 
      cells and 2) characterize the role of metal-transferrin complexes in the 
      regulation of these receptors. TFR expression was altered by 1) incubation with 
      metal-transferrin (Tf) complexes, 2) TFR1 and TFR2 small interfering RNA 
      knockdown, and 3) transfection with a human TFR2 plasmid. TBI uptake was measured 
      using (59)Fe-(125)I-labeled Tf and mRNA and protein expression by real-time PCR 
      and Western blot analysis, respectively. Fe(2)Tf, Co(2)Tf, and Mn(2)Tf increased 
      TFR2 protein expression, indicating that the upregulation was not specifically 
      regulated by iron-transferrin but also other metal-transferrins. In addition, 
      Co(2)Tf and Mn(2)Tf upregulated TFR1, reduced ferritin, and increased 
      hypoxia-inducible factor-1alpha protein expression, suggesting that TFR1 
      upregulation was due to a combination of iron deficiency and chemical hypoxia. 
      TBI uptake correlated with changes in TFR1 but not TFR2 expression. TFR1 
      knockdown reduced iron uptake by 80% while TFR2 knockdown did not affect uptake. 
      At 5 microM transferrin, iron uptake was not affected by combined TFR1 and TFR2 
      knockdown. Transfection with a hTFR2 plasmid increased TFR2 protein expression, 
      causing a 15-20% increase in iron uptake and ferritin levels. This shows for the 
      first time that TFR-mediated TBI uptake is mediated primarily via TFR1 but not 
      TFR2 and that a high-capacity TFR-independent pathway exists in hepatoma cells.
FAU - Herbison, Carly E
AU  - Herbison CE
AD  - The Univ. of Western Australia, Fremantle Hospital, Australia.
FAU - Thorstensen, Ketil
AU  - Thorstensen K
FAU - Chua, Anita C G
AU  - Chua AC
FAU - Graham, Ross M
AU  - Graham RM
FAU - Leedman, Peter
AU  - Leedman P
FAU - Olynyk, John K
AU  - Olynyk JK
FAU - Trinder, Debbie
AU  - Trinder D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091014
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antigens, CD)
RN  - 0 (CD71 antigen)
RN  - 0 (Metals)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (TFR2 protein, human)
RN  - 0 (Transferrin)
RN  - 3G0H8C9362 (Cobalt)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Antigens, CD/genetics/*metabolism
MH  - Carcinoma, Hepatocellular/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cobalt/metabolism
MH  - Humans
MH  - Iron/*metabolism/pharmacokinetics
MH  - Liver Neoplasms/*metabolism/pathology
MH  - Metals/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Transferrin/genetics/*metabolism
MH  - Transfection
MH  - Transferrin/*metabolism
MH  - Up-Regulation
EDAT- 2009/10/16 06:00
MHDA- 2009/12/30 06:00
CRDT- 2009/10/16 06:00
PHST- 2009/10/16 06:00 [entrez]
PHST- 2009/10/16 06:00 [pubmed]
PHST- 2009/12/30 06:00 [medline]
AID - ajpcell.00649.2008 [pii]
AID - 10.1152/ajpcell.00649.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Dec;297(6):C1567-75. doi: 
      10.1152/ajpcell.00649.2008. Epub 2009 Oct 14.