Abstract

Project 3 Acellular Hb in the circulation has been proposed to be a major source of toxicity and poor outcome for transfusions involving either aged RBCs or HBOCs. One of the major overall objectives of this program project is to test the hypothesis that acellular Hbs contribute to these poor outcomes due to depletion of endothelium-generated NO and that acellular Hb toxicity can be reversed through compensatory mechanisms that generate bioactive NO. Project 3 in conjunction with the other projects will: i) determine the role of bioactive NO in the creation or exacerbation of acellular Hb induced toxicities; and ii) establish of the role of released or nitrite-generated bioactive NO in preventing, limiting, or ameliorating acellular Hb toxicities. Project 3 will contribute to these objectives through the following three

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL110900-02
Application #
8517808
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$391,432
Indirect Cost
$157,042

  Institution

Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Kettisen, Karin; Strader, Michael Brad; Wood, Francine et al. (2018) Site-directed mutagenesis of cysteine residues alters oxidative stability of fetal hemoglobin. Redox Biol 19:218-225
Alayash, Abdu I (2018) Oxidative pathways in the sickle cell and beyond. Blood Cells Mol Dis 70:78-86
Wallace, Martina; Green, Courtney R; Roberts, Lindsay S et al. (2018) Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues. Nat Chem Biol 14:1021-1031
Sjodt, Megan; Macdonald, Ramsay; Marshall, Joanna D et al. (2018) Energetics underlying hemin extraction from human hemoglobin by Staphylococcus aureus. J Biol Chem 293:6942-6957
Jana, Sirsendu; Strader, Michael Brad; Meng, Fantao et al. (2018) Hemoglobin oxidation-dependent reactions promote interactions with band 3 and oxidative changes in sickle cell-derived microparticles. JCI Insight 3:
Bissé, Emmanuel; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain et al. (2017) Hemoglobin Kirklareli (? H58L), a New Variant Associated with Iron Deficiency and Increased CO Binding. J Biol Chem 292:2542-2555
Jani, Vivek P; Jelvani, Alborz; Moges, Selamawit et al. (2017) Polyethylene Glycol Camouflaged Earthworm Hemoglobin. PLoS One 12:e0170041
Alayash, Abdu I (2017) Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help? Biomolecules 7:
Meng, Fantao; Alayash, Abdu I (2017) Determination of extinction coefficients of human hemoglobin in various redox states. Anal Biochem 521:11-19
Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat et al. (2017) HbE/?-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics. Antioxid Redox Signal 26:794-813

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