Heme-oxygenases during erythropoiesis in K562 and human bone marrow cells.
Heme-oxygenases during erythropoiesis in K562 and human bone marrow cells.
复制标题
DOI：
10.1371/journal.pone.0021358
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Maya-Monteiro CM
中科院分区：
文献类型：
--
作者：
Alves LR;Costa ES;Sorgine MH;Nascimento-Silva MC;Teodosio C;Bárcena P;Castro-Faria-Neto HC;Bozza PT;Orfao A;Oliveira PL;Maya-Monteiro CM
在哺乳动物细胞中，血红素可被血红素加氧酶（HO）降解。血红素加氧酶1（HO-1）是血红素诱导型同工酶，而血红素加氧酶2（HO-2）是组成型酶。在这里，我们研究了在人骨髓红系前体细胞和K562细胞的红系分化过程中HO的存在。K562细胞HO-1 mRNA和蛋白表达水平低于检测限。此外，血红素不能诱导HO-1，在蛋白质和mRNA的轮廓。令人惊讶的是，HO-2的表达被抑制后，与血红素孵育。为了评估这些发现的生理相关性，我们分析了正常人骨髓红细胞生成过程中HO的表达。红系前体细胞的特点是缺乏显着的HO-1的表达和HO-2在分化过程中进行性减少。FLVCR的表达，最近描述的血红素出口红系前体细胞中发现，也进行了分析。有趣的是，HO解毒系统的中断伴随着FLVCR的瞬时诱导。这将是有趣的，以验证如果HO表达的抑制，我们发现，是防止一个无用的循环，伴随血红素合成和catalysts。我们认为，红细胞生成的一个重要特征可能是血红素输出替代血红素分解，作为防止血红素毒性的机制。
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.
登录
查看更多内容
DOI：
10.3324/haematol.13359
发表时间：
2008-11-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Rey, Michelle A.;Duffy, Simon P.;Tailor, Chetankumar S.
通讯作者：
Tailor, Chetankumar S.
影响因子：
2.6
作者：
Lammers, R;Giesert, C;Bühring, HJ
通讯作者：
Bühring, HJ
影响因子：
64.8
作者：
RUTHERFORD, TR;CLEGG, JB;WEATHERALL, DJ
通讯作者：
WEATHERALL, DJ
影响因子：
6.5
作者：
IBRAHIM, NG;LUTTON, JD;LEVERE, RD
通讯作者：
LEVERE, RD
影响因子：
20.3
作者：
LOZZIO, CB;LOZZIO, BB
通讯作者：
LOZZIO, BB