title: Hemopexin decreases hemin accumulation and catabolism by neural cells.
abstract: Hemopexin is a serum, CSF, and neuronal protein that is protective after experimental stroke. Its efficacy in the latter has been linked to increased expression and activity of heme oxygenase (HO)-1, suggesting that it facilitates heme degradation and subsequent release of cytoprotective biliverdin and carbon monoxide. In this study, the effect of hemopexin on the rate of hemin breakdown by CNS cells was investigated in established in vitro models. Equimolar hemopexin decreased hemin breakdown, as assessed by gas chromatography, by 60-75% in primary cultures of murine neurons and glia. Extracellular hemopexin reduced cell accumulation of ⁵⁵Fe-hemin by over 90%, while increasing hemin export or extraction from membranes by fourfold. This was associated with significant reduction in HO-1 expression and neuroprotection. In a cell-free system, hemin breakdown by recombinant HO-1 was reduced over 80% by hemopexin; in contrast, albumin and two other heme-binding proteins had no effect. Although hemopexin was detected on immunoblots of cortical lysates from adult mice, hemopexin knockout per se did not alter HO activity in cortical cells treated with hemin. These results demonstrate that hemopexin decreases the accumulation and catabolism of exogenous hemin by neural cells. Its beneficial effect in stroke models is unlikely to be mediated by increased production of cytoprotective heme breakdown products.
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, College Building Room 813, Philadelphia, PA 19107, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen-Roetling
authors.forename: Wenpei
authors.initials: W
authors.lastname: Liu
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Regan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002849:Chromatography, Gas; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism; D006427:Hemin / Q000378:metabolism*; D006466:Hemopexin / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*
chemical_list: D006427:Hemin; D006466:Hemopexin; D051547:Heme Oxygenase-1