Abstract

Our laboratory has focused on understanding the mechanisms controlling acellular Hbs oxidative and nitrosafive toxicities in vitro and in vivo. Evidence is accumulating which suggests that reduction-oxidation """"""""redox"""""""" reactions of free Hb and hemoglobin-based oxygen carriers (HBOCs), also known as """"""""blood substitutes"""""""" do occur in vivo with some potentially serious clinical consequences. A primary focus of the research is based on the role of oxidants-mediated changes in acellular Hb under conditions that can mimic ischemia/reperfusion injury. Depending on whether host endogenous reductive mechanisms are employed or not, we will invesfigate Hb oxidative reactions in vivo using rats (ascorbate producing) or guinea pigs (ascorbate non-producing). The role of haptoglobin (Hp) and/or other antioxidant materials in supplemenfing endogenous antioxidant mechanisms will be invesfigated. For the investigation of effects of oxygen carrying HBOCs on cardiac

  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 #
8517812
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
$188,972
Indirect Cost

  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:
Strader, Michael Brad; Alayash, Abdu I (2017) Exploring Oxidative Reactions in Hemoglobin Variants Using Mass Spectrometry: Lessons for Engineering Oxidatively Stable Oxygen Therapeutics. Antioxid Redox Signal 26:777-793
Alayash, Abdu I (2017) Mechanisms of Toxicity and Modulation of Hemoglobin-Based Oxygen Carriers (HBOCs). Shock :
Kassa, Tigist; Strader, M B; Nakagawa, Akito et al. (2017) Targeting ?Cys93 in hemoglobin S with an antisickling agent possessing dual allosteric and antioxidant effects. Metallomics 9:1260-1270
Martucci, Alexandre Fabricio; Abreu Martucci, Ana Carolina Carvalho Ferreira; Cabrales, Pedro et al. (2017) Acute kidney function and morphology following topload administration of recombinant hemoglobin solution. Artif Cells Nanomed Biotechnol 45:24-30
Jana, Sirsendu; Meng, Fantao; Hirsch, Rhoda E et al. (2017) Oxidized Mutant Human Hemoglobins S and E Induce Oxidative Stress and Bioenergetic Dysfunction in Human Pulmonary Endothelial Cells. Front Physiol 8:1082

Showing the most recent 10 out of 105 publications