Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites’ Inhibition of Erythroid Progenitor Growth

Figures

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  Figure 1. Nitric oxide derivatives in plasma of mouse peripheral blood. After 7 days of in vivo treatment by hydroxyurea (HU) (A), sodium nitrite (NO2) and sodium nitrate (NO3) (B,C), with or without PTIO, nitrate (NO3) level (A,B) and total NO level (NOx) (A,C) were determined. Values are mean ± SEM (n = 6). * p < 0.05, ** p < 0.01, vs. non-treated mice (Control); # p < 0.05 vs. HU (A) or PTIO (C) treated only.

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  Figure 2. Quantity of bone marrow nucleated cells per femur of mice. After 7 days of in vivo treatment by hydroxyurea (HU) (A), sodium nitrite (NO2) or sodium nitrate (NO3) (B) with or without PTIO. Values are mean ± SEM (n = 10). ** p < 0.01 and *** p < 0.001 vs. non-treated mice (Control); ## p < 0.01 vs. NO2 or NO3 treated only.

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  Figure 3. Myeloid progenitor growth of mouse bone marrow origin. Number of ex vivo BFU-E (A,B), CFU-E (C,D), and CFU-GM (E,F) colonies of mice treated with hydroxyurea (HU) (A,C,E), sodium nitrite (NO2), and sodium nitrate (NO3) (B,D,F) with or without PTIO. Values are mean ± SEM (n = 10). * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. non-treated mice (Control); # p < 0.05, and ### p < 0.001 vs. HU (A,C) or NO3 (B,F) treated only.

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  Figure 4. NOS levels in mouse bone marrow derived mononuclear cells (BMC). Frequency of eNOS (A,B), nNOS (C,D), and iNOS (E,F) positive BMC in mice in vivo treated with hydroxyurea (HU) (A,C,E), sodium nitrite (NO2), and sodium nitrate (NO3) (B,D,F), with or without PTIO. The correspond immunocytochemistry slides are in Supplemental Figure S1. Values are mean ± SEM (n = 10). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. non-treated mice (Control); # p < 0.05, and ## p < 0.01 vs. HU or NO2 treated only.

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  Figure 5. NOS levels in mouse ex vivo CFU-E colonies. Frequency of eNOS (A,B) and iNOS (C,D) positive cells in mice in vivo treated with hydroxyurea (HU) (A,C), sodium nitrite (NO2), and sodium nitrate (NO3) (B,D), with or without PTIO. The corresponding immunocytochemistry slides are in Supplemental Figure S2. Values are mean ± SEM (n = 5). * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. non-treated mice (Control); ## p < 0.01 and ### p < 0.001 vs. HU or NO2/NO3 treated only.

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  Figure 6. NOS levels in mouse ex vivo BFU-E/CFU-GM colonies. Frequency of eNOS positive cells in mice in vivo treated with hydroxyurea (A), sodium nitrite (NO2), and sodium nitrate (NO3) (B), with or without PTIO. Frequency of nNOS positive cells in mice treated with hydroxyurea (C) with or without PTIO. The correspond immunocytochemistry slides are in Supplemental Figure S3. Values are mean ± SEM (n = 5). ** p < 0.01 and *** p < 0.001 vs. non-treated mice (Control); ## p < 0.01 vs. HU treated only.

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  Scheme 1. Nitrate (NO3), nitrite (NO2) and hydroxyurea (HU) effects on myeloid differentiation and frequency of NOS isoforms in myeloid progenitors.