ArticleExperimental hematology2009
Mechanistic studies on the effects of nicotinamide on megakaryocytic polyploidization and the roles of NAD+ levels and SIRT inhibition.
Article in Experimental hematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- miR-486-5p and miR-22-3p Enable Megakaryocytic Differentiation of Hematopoietic Stem and Progenitor Cells without Thrombopoietin.International journal of molecular sciences · 2022Article
- A derivative of vitamin BScientific reports · 2021Article
- Generation and manipulation of human iPSC-derived platelets.Cellular and molecular life sciences : CMLS · 2021Review
- Mitochondrial dynamics and reactive oxygen species initiate thrombopoiesis from mature megakaryocytes.Blood advances · 2021Article
- The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies.International journal of molecular sciences · 2021Review
- Molecular and functional characteristics of megakaryocytes and platelets in aging.Current opinion in hematology · 2020Review
- NADNature metabolism · 2020Review
- Induction of differentiation of human stem cellsWorld journal of stem cells · 2019Review
- Megakaryocyte lineage development is controlled by modulation of protein acetylation.PloS one · 2018Article
- Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations.PloS one · 2017Article
- SIRT1 is a critical regulator of K562 cell growth, survival, and differentiation.Experimental cell research · 2016Article
- Hoxa10 null animals exhibit reduced platelet biogenesis.British journal of haematology · 2016Article
- Manipulating megakaryocytes to manufacture platelets ex vivo.Journal of thrombosis and haemostasis : JTH · 2015Review
- Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation.Biotechnology and bioengineering · 2014Article
- Profiling deacetylase activities in cell lysates with peptide arrays and SAMDI mass spectrometry.Analytical chemistry · 2013Article
- Synergistic effect of hydrogen peroxide on polyploidization during the megakaryocytic differentiation of K562 leukemia cells by PMA.Experimental cell research · 2013Article
- Three-stage ex vivo expansion of high-ploidy megakaryocytic cells: toward large-scale platelet production.Tissue engineering. Part A · 2013Article
- Administration of nicotinamide does not increase platelet levels in mice.Blood cells, molecules & diseases · 2013Article
- Epigenetic contributions in the development of rheumatoid arthritis.Arthritis research & therapy · 2012Review
- Proposed megakaryocytic regulon of p53: the genes engaged to control cell cycle and apoptosis during megakaryocytic differentiation.Physiological genomics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveMegakaryocytic cells (Mks) undergo endomitosis and become polyploid. Mk ploidy correlates with platelet production. We previously showed that nicotinamide (NIC) greatly increases Mk ploidy in cultures of human mobilized peripheral blood CD34(+) cells. This study aims to examine the generality of NIC effects, NIC's impact on Mk ultrastructure, and potential mechanisms for the increased ploidy. MATERIALS AND
methodsWe used electron microscopy to examine Mk ultrastructure and flow cytometry to evaluate NIC effects on Mk differentiation and ploidy in mobilized peripheral blood CD34(+) cell cultures under diverse megakaryopoietic conditions. Mk ploidy and NAD(H) content were evaluated for NIC and other NAD(+) precursors. We tested additional inhibitors of the sirtuin (or SIRT) 1 and SIRT2 histone/protein deacetylases and, after treatment with NIC, evaluated changes in the acetylation of SIRT1/2 targets.
resultsNIC increased ploidy under diverse culture conditions and did not alter Mk ultrastructure; 6.25 mM NIC increased NAD(+) levels fivefold. Quinolinic acid increased NAD(+) similar to that for 1 mM NIC, but yielded a much smaller ploidy increase. Similar increases in Mk ploidy were obtained using NIC or the SIRT1/2 inhibitor cambinol, while the SIRT2 inhibitor AGK2 moderately increased ploidy. SIRT1/2 inhibition in cells treated with NIC was evidenced by increased acetylation of nucleosomes and p53. Greater p53 acetylation with NIC was associated with increased binding of p53 to its consensus DNA binding sequence.
conclusionNIC greatly increases Mk ploidy under a wide range of conditions without altering Mk morphology. Inhibition of SIRT1 and/or SIRT2 is primarily responsible for NIC effects on Mk maturation.
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