title: Plasma protein haptoglobin modulates renal iron loading.
abstract: Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Turin, Via Santena 5bis, 10126 Turin, Italy.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.forename: Jakub
authors.initials: J
authors.lastname: Gburek
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
authors.forename: Samuele
authors.initials: S
authors.lastname: Marro
authors.forename: Soren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Laurberg
authors.forename: Erik I
authors.initials: EI
authors.lastname: Christensen
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
mesh_terms: D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D006242:Haptoglobins / Q000032:analysis / Q000172:deficiency / Q000378:metabolism*; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology; D008297:Male; D051379:Mice; D008954:Models, Biological; D009132:Muscles / Q000293:injuries; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D006242:Haptoglobins; D007501:Iron