title: Oxygenation properties and oxidation rates of mouse hemoglobins that differ in reactive cysteine content.
abstract: House mice (genus Mus) harbor extensive allelic variation at two tandemly duplicated genes that encode the β-chain subunits of adult hemoglobin (Hb). Alternative haplotypes differ in the level of sequence divergence between the two β-globin gene duplicates: the Hbb(d) and Hbb(p) haplotypes harbor two structurally distinct β-globin genes, whereas the Hbb(s) haplotype harbors two β-globin duplicates that are identical in sequence. One especially salient difference between the s-type Hbs relative to the d- and p-type Hbs relates to the number of reactive β-chain cysteine residues. In addition to the highly conserved cysteine residue at β93, the d- and p-type Hbs contain an additional reactive cysteine residue at β13. To assess the functional consequences of allelic variation in β-globin cysteine content, we measured O(2)-binding properties and H(2)O(2)-induced oxidation rates of mono- and dicysteinyl β-Hbs from 4 different inbred strains of mice: C57BL/6J, BALB/cJ, MSM/Ms, and CAROLI/EiJ. The experiments revealed that purified Hbs from the various mouse strains did not exhibit substantial variation in O(2)-binding properties, but s-type Hb (which contains a single reactive β-chain cysteine residue) was far more readily oxidized to Fe(3+) metHb by H(2)O(2) than other mouse Hbs that contain two reactive β-chain cysteine residues. These results suggest that the possession of an additional reactive cysteine residue may protect against metHb formation under oxidizing conditions. The allelic differences in β-globin cysteine content could affect aspects of redox signaling and oxidative/nitrosative stress responses that are mediated by Hb-S-nitrosylation and Hb-S-glutathionylation pathways.
authors: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA. jstorz2@unl.edu
authors: Jay F
authors: JF
authors: Storz
authors: Roy E
authors: RE
authors: Weber
authors: Angela
authors: A
authors: Fago
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D016415:Sequence Alignment; D055544:beta-Globins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D055544:beta-Globins; D003545:Cysteine; D010100:Oxygen