Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/47652
Title: MECHANISMS FOR REGULATION OF REDOX-ACTIVE HEMOGLOBIN
Authors: NEHA BAHL
Keywords: lipopolysaccharide, infection, tissue factor, coagulation, blood substitutes, hb peptides
Issue Date: 24-Aug-2012
Source: NEHA BAHL (2012-08-24). MECHANISMS FOR REGULATION OF REDOX-ACTIVE HEMOGLOBIN. ScholarBank@NUS Repository.
Abstract: Extracellular hemoglobin (Hb) resulting from microbial hemolytic activity or coagulation-mediated inflammation is toxic owing to its redox activity. We sought to explore mechanisms for regulation of redox-active Hb via introduction of protein modifications and identification of endogenous antioxidant mechanisms. Bacterial lipopolysaccharide (LPS) amplifies the redox activity of Hb, which generates free radicals that aid antimicrobial defense. Computational analysis of Hb identified LPS-binding hotspots, which were further defined via peptide-based binding assays and confirmed by mutagenesis of Hb subunits. Mutations suppressed the LPS-induced augmentation of the redox activity of Hb subunits. Tissue factor (TF), a coagulation initiator, competed with LPS for binding Hb, and desensitized the redox activity of Hb towards LPS. Furthermore, Hb preserved the procoagulant activity of TF, thus uncovering a novel link between coagulation and immunity. Our findings may steer bioengineering of Hb towards the design of safer blood substitutes, with minimal risks of endotoxicity and redox reactivity.
URI: http://scholarbank.nus.edu.sg/handle/10635/47652
Appears in Collections:Ph.D Theses (Open)

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