The anemia of "haemoglobin-deficit" (hbd/hbd) mice is caused by a defect in transferrin cycling

Experimental Hematology
An-Sheng ZhangPrem Ponka

Abstract

The hemoglobin-deficit mouse mutant (hbd) is characterized by a hypochromic, microcytic anemia that is inherited in an autosomal, recessive manner. The recently identified gene responsible, Sec15l1, is specific to hematopoietic stem cells and is homologous to a gene encoding a member of the exocyst pathway in yeast. However, the defective cellular mechanism underlying the hemoglobin deficiency in hbd/hbd mice has not been functionally identified. Here we investigated the possibility that erroneous transferrin trafficking is responsible for the hbd phenotype. Reticulocytes were harvested from hbd/hbd mice and from background- and age-matched controls. Iron and transferrin uptake and iron utilization experiments were performed using 59Fe- or 125I-transferrin to follow the trafficking and utilization of the protein and metal. Compared to controls, iron and transferrin uptake as well as iron incorporation into heme was compromised in hbd reticulocytes. Importantly, reduced heme synthesis in these cells was restored to normal values by using an iron source that bypasses the transferrin-receptor pathway. We also found that +/+ and hbd reticulocytes take up free, ferrous iron at identical rates, while the rates of Tf internalization a...Continue Reading

References

Apr 1, 1988·British Journal of Haematology·A Egyed
Nov 1, 1986·Journal of Cellular Physiology·J D LaskeyH M Schulman
May 1, 1986·Proceedings of the Society for Experimental Biology and Medicine·R M BannermanJ A Edwards
Apr 21, 1972·Biochimica Et Biophysica Acta·J Martinez-Medellin, H M Schulman
Apr 1, 1997·The Journal of Clinical Investigation·H TsukaguchiM A Hediger
Mar 14, 1997·Biochimica Et Biophysica Acta·D R Richardson, P Ponka
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y KeeR H Scheller
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·M D FlemingN C Andrews
Aug 10, 2001·Experimental Hematology·J Palis, M C Yoder
Sep 26, 2001·Bone Marrow Transplantation·G LucarelliE Angelucci
Oct 1, 1959·Biochimica Et Biophysica Acta·F W TEALE
Aug 11, 2005·Pflügers Archiv : European journal of physiology·Bryan MackenzieMatthias A Hediger
Oct 18, 2005·Nature Genetics·Jackie E LimNancy C Andrews

❮ Previous
Next ❯

Citations

Dec 10, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Des R RichardsonYohan Suryo Rahmanto
May 25, 2010·Proceedings of the National Academy of Sciences of the United States of America·Des R RichardsonPrem Ponka
May 7, 2011·Antioxidants & Redox Signaling·Michael Li-Hsuan HuangDes R Richardson
Mar 23, 2011·Current Opinion in Hematology·Paul A Ney
Aug 1, 2009·Development, Growth & Differentiation·Krzysztof WandzikHendrik Fuchs
Aug 7, 2013·Nutrients·Andrea U Steinbicker, Martina U Muckenthaler
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Michael Li-Hsuan HuangDes R Richardson
May 10, 2011·Annual Review of Nutrition·Robert E FlemingRobert S Britton
Feb 3, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Gregory J AndersonDavid M Frazer
Jan 9, 2009·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Deepak Darshan, Gregory J Anderson
Jun 2, 2009·Cellular and Molecular Life Sciences : CMLS·Gregory Jon Anderson, Christopher D Vulpe
Apr 7, 2009·Biochimica Et Biophysica Acta·Michael D Garrick, Laura M Garrick
Dec 30, 2006·Trends in Cell Biology·Louise L DunnDes R Richardson
Jan 31, 2012·Biochimica Et Biophysica Acta·Caiyong Chen, Barry H Paw
Aug 23, 2011·Biochimica Et Biophysica Acta·Alex D SheftelPrem Ponka
Jun 24, 2015·Science China. Life Sciences·FengXiu SunCaiYong Chen
Feb 19, 2013·Cell Metabolism·Caiyong ChenBarry H Paw
Nov 29, 2016·Antioxidants & Redox Signaling·Viktoria KuhnMiriam M Cortese-Krott
Dec 19, 2018·Pharmaceuticals·Nyamdelger Sukhbaatar, Thomas Weichhart
Nov 8, 2006·Biochimica Et Biophysica Acta·Michael D Garrick, Laura M Garrick

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.