title: Heme-oxygenases during erythropoiesis in K562 and human bone marrow cells.
abstract: In mammalian cells, heme can be degraded by heme-oxygenases (HO). Heme-oxygenase 1 (HO-1) is known to be the heme inducible isoform, whereas heme-oxygenase 2 (HO-2) is the constitutive enzyme. Here we investigated the presence of HO during erythroid differentiation in human bone marrow erythroid precursors and K562 cells. HO-1 mRNA and protein expression levels were below limits of detection in K562 cells. Moreover, heme was unable to induce HO-1, at the protein and mRNA profiles. Surprisingly, HO-2 expression was inhibited upon incubation with heme. To evaluate the physiological relevance of these findings, we analyzed HO expression during normal erythropoiesis in human bone marrow. Erythroid precursors were characterized by lack of significant expression of HO-1 and by progressive reduction of HO-2 during differentiation. FLVCR expression, a recently described heme exporter found in erythroid precursors, was also analyzed. Interestingly, the disruption in the HO detoxification system was accompanied by a transient induction of FLVCR. It will be interesting to verify if the inhibition of HO expression, that we found, is preventing a futile cycle of concomitant heme synthesis and catabolism. We believe that a significant feature of erythropoiesis could be the replacement of heme breakdown by heme exportation, as a mechanism to prevent heme toxicity.
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Liliane R
authors.initials: LR
authors.lastname: Alves
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Costa
authors.forename: Marcos H F
authors.initials: MH
authors.lastname: Sorgine
authors.forename: Maria Clara L
authors.initials: MC
authors.lastname: Nascimento-Silva
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodosio
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Oliveira
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Maya-Monteiro
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004920:Erythropoiesis / Q000187:drug effects; D006021:Glycophorins / Q000378:metabolism; D006418:Heme / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D020014:K562 Cells; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011991:Receptors, Virus / Q000378:metabolism
chemical_list: C492690:FLVCR1 protein, human; C409972:GYPA protein, human; D006021:Glycophorins; D006454:Hemoglobins; D026901:Membrane Transport Proteins; D011991:Receptors, Virus; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2