| Autor: |
Smith A; Division of Molecular Biology & Biochemistry, School of Biological Sciences, University of Missouri-K.C., 5007 Rockhill Road, Kansas City, MO 64110, USA. smithan@umkc.edu, Rish KR, Lovelace R, Hackney JF, Helston RM |
| Jazyk: |
angličtina |
| Zdroj: |
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine [Biometals] 2009 Jun; Vol. 22 (3), pp. 421-37. Date of Electronic Publication: 2008 Nov 28. |
| DOI: |
10.1007/s10534-008-9178-z |
| Abstrakt: |
Hemopexin (HPX) binds heme tightly, thus protecting cells from heme toxicity during hemolysis, trauma and ischemia-reperfusion injury. Heme uptake via endocytosis of heme-HPX followed by heme catabolism by heme oxygenase-1 (HMOX1) raises regulatory iron pools, thus linking heme metabolism with that of iron. Normal iron homeostasis requires copper-replete cells. When heme-HPX induces HMOX1, the copper-storing metallothioneins (MTs) are also induced whereas the copper-responsive copper chaperone that delivers copper to Cu, Zn superoxide dismutase, CCS1, is decreased; both are known responses when cellular copper levels rise. Endocytosis of heme-HPX is needed to regulate CCS1 since the signaling ligand cobalt-protoporphyrin (CoPP)-HPX, which does not induce HMOX1 but does co-localize with heme-HPX in endosomes, also decreased CCS1. These observations support that heme-HPX mobilizes copper in cells. The regulation of both hmox1 and mt1 is prevented by the copper-chelator, bathocuproinedisulfonate (BCDS), but not uptake of heme-AlexaFluor-labeled HPX into endosomes. Supporting a role for copper in HMOX1 regulation by heme-HPX, nutritional copper deficiency generated by tetraethylene pentamine or 232 tetraamine prevented HMOX1 induction. Using conditions that mimic maturing endosomes, we found that copper prevents rebinding of heme to apo-HPX. A model is presented in which copper endocytosis together with that of heme-HPX provides a means to facilitate heme export from HPX in the maturing endosomes: heme is needed for hmox1 transcription, while cytosolic copper and CCS1 provide a link for the known simultaneous regulation of hmox1 and mt1 by heme-HPX. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full text from SpringerLink