Heme-oxygenases During Erythropoiesis in K562 and Human Bone Marrow Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Jul 19

PMID 21765894

Citations 11

Authors

Liliane R Alves

Elaine S Costa

Marcos H F Sorgine

Maria Clara L Nascimento-Silva

Cristina Teodosio

Paloma Barcena

Hugo C Castro-Faria-Neto

Patricia T Bozza

Alberto Orfao

Pedro L Oliveira

Clarissa M Maya-Monteiro

Affiliations

Soon will be listed here.

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.

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