Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy

Document identifier: oai:DiVA.org:ltu-7657
Access full text here:10.1182/blood-2008-12-195883
Keyword: Natural Sciences, Earth and Related Environmental Sciences, Geochemistry, Naturvetenskap, Geovetenskap och miljövetenskap, Geokemi, Applied Geology, Tillämpad geologi
Publication year: 2009
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Abstract:

Megakaryocytes (MKs) undergo an endomitotic cell cycle, leading to polyploidy. We examined the expression of the flavoproteins and oxidative stress-promoting enzymes, NADPH oxidases (Nox's), in MKs because of their known role in promoting the cell cycle. Although the expression of Nox isoforms varies between cell types, they are induced at the mRNA level by mitogenic stimuli. Western blotting or reverse transcription-polymerase chain reaction of purified mouse MKs isolated from thrombopoietin (TPO)-treated bone marrow (BM) cultures indicated high expression of Nox1, a weak expression of Nox4, and no significant expression of Nox2. Immunofluorescence of freshly isolated MKs confirmed strong expression of Nox1 in one-third of MKs, whereas Nox1 staining was detected in nearly all MKs in TPO-stimulated BM cultures. Treatment of mouse BM cultures with Nox inhibitors resulted in accumulation of MKs with low DNA content levels and significant reduction of higher ploidy MKs. Purified, Nox-inhibited MKs showed a notable decrease in the level of the G1 phase cyclin E, a cyclin associated with MK polyploidy, and its up-regulation restored most of the effect of Nox inhibitors. Hence, this study shows the expression of Nox isoforms in MKs and highlights a potential role of flavoproteins in promoting polyploidization in this lineage

Authors

Donald J. McCrann

Boston University School of Medicine
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Alexia Eliades

Boston University School of Medicine
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Maria Mäkitalo

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Kuniharu Matsuno

Kyoto Prefectural University of Medicine
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Katya Ravid

Boston University School of Medicine
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