Oxygenation properties and oxidation rates of mouse hemoglobins that differ in reactive cysteine content

Jay F. Storz, Roy E. Weber, Angela Fago

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 2O 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 2O 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.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalComparative Biochemistry and Physiology - A Molecular and Integrative Physiology
Volume161
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Oxygenation
Cysteine
Hemoglobins
Globins
Oxidation
Ports and harbors
Haplotypes
Sickle Hemoglobin
Genes
Hemoglobin Subunits
Duplicate Genes
Inbred Strains Mice
Oxidative stress
Oxidation-Reduction
Oxidative Stress

Keywords

  • Globins
  • Hemoglobin
  • Met-hemoglobin
  • Mus
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

Cite this

Oxygenation properties and oxidation rates of mouse hemoglobins that differ in reactive cysteine content. / Storz, Jay F.; Weber, Roy E.; Fago, Angela.

In: Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology, Vol. 161, No. 2, 01.02.2012, p. 265-270.

Research output: Contribution to journalArticle

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