Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy
Document identifier: oai:DiVA.org:ltu-7657
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10.1182/blood-2008-12-195883Keyword: Natural Sciences,
Earth and Related Environmental Sciences,
Geochemistry,
Naturvetenskap,
Geovetenskap och miljövetenskap,
Geokemi,
Applied Geology,
Tillämpad geologiPublication year: 2009Relevant Sustainable Development Goals (SDGs):
The SDG label(s) above have been assigned by OSDG.aiAbstract: 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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>>
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identifier: oai:DiVA.org:ltu-7657
datestamp: 2021-04-19T11:01:45Z
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10.1182/blood-2008-12-195883
60f55370-b9af-11df-a707-000ea68e967b
titleInfo:
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lang: eng
title: Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy
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
subject:
@attributes:
lang: eng
authority: uka.se
topic:
Natural Sciences
Earth and Related Environmental Sciences
Geochemistry
@attributes:
lang: swe
authority: uka.se
topic:
Naturvetenskap
Geovetenskap och miljövetenskap
Geokemi
@attributes:
lang: eng
authority: ltu
topic: Applied Geology
genre: Research subject
@attributes:
lang: swe
authority: ltu
topic: Tillämpad geologi
genre: Research subject
language:
languageTerm: eng
genre:
publication/journal-article
ref
note:
Published
5
Upprättat; 2009; 20100906 (makmar)
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McCrann
Donald J.
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affiliation: Boston University School of Medicine
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Eliades
Alexia
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affiliation: Boston University School of Medicine
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Mäkitalo
Maria
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Matsuno
Kuniharu
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roleTerm: aut
affiliation: Kyoto Prefectural University of Medicine
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Ravid
Katya
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roleTerm: aut
affiliation: Boston University School of Medicine
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dateIssued: 2009
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titleInfo:
title: Blood
identifier:
0006-4971
1528-0020
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number: 114
@attributes:
type: issue
number: 6
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start: 1243
end: 1249
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