title: Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia-inducible factor-1 alpha.
abstract: Apo-form of human lactoferrin (LF) is a potent iron chelator, this feature being similar to the iron-binding properties of a synthetic chelator desferoxamine (DFO). The latter stabilizes the principal adaptive transcriptional hypoxia-inducible factor-1 alpha (HIF-1α). Since DFO is known as a pharmacological mimetic of hypoxia it was decided to test whether apo-LF is able to perform as such. Mice either injected intraperitoneally or given per os apo-LF displayed HIF-1α in liver, lungs, heart, brain, spleen and kidneys, as judged by results of Western blotting. Similar administration of iron-saturated LF (75 mg/kg) did not bring forth such effect. Synthesis of erythropoietin and ceruloplasmin became increased in the first case, which is explained by the respective genes being targets for HIF-1α. Apo-LF, but not Fe-LF, injected intraperitoneally to hypoxia low-resistant mice 24 h before animals were subjected to normobaric hypoxia with hypercapnia caused a significant increase of life-time by 40 %. The results obtained show that, like DFO, apo-LF performs as a normoxic mimetic of hypoxia, capable of stabilizing HIF-1α. Protective features of LF and DFO and their pharmacological properties involving HIF-1α are discussed.
authors.affiliation: Institute for Experimental Medicine, N-W Branch of the Russian Academy of Medical Sciences, Pavlov Street 12, Saint-Petersburg, 197376, Russia.
authors.forename: Elena T
authors.initials: ET
authors.lastname: Zakharova
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Kostevich
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sokolov
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
mesh_terms: D001059:Apoproteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001059:Apoproteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C039223:apolactoferrin; D007781:Lactoferrin