Anion exchange through band 3 protein in canine leishmaniasis at different stages of disease

Pflugers Arch. 2017 Jun;469(5-6):713-724. doi: 10.1007/s00424-017-1974-2. Epub 2017 Apr 5.

Abstract

Band 3 protein efficiency in mediating Cl-/HCO3- exchange through erythrocytes membrane is reduced by oxidative stress. The aim of the present study was to verify whether and how anion transport through band 3 protein may be useful in monitoring canine leishmaniasis (Leishmania infantum) development, a disease associated to membrane protein degradation and oxidative stress. To accomplish this aim, serological analysis to determine IFAT (immunofluorescence antibody test) titers against leishmaniasis has been performed and 1:160 and 1:540 titers, determined at diagnosis and after 6 months, were considered for experiments. Oxidative conditions have been assessed by estimating MDA (malondialdehyde) plasma levels, intracellular GSH (reduced glutathione) content, and membrane -SH groups. Band 3 protein anion exchange capability was evaluated by measuring the rate constant for SO4= uptake, and its expression levels, along with those of P-Tyr (phosphorylated tyrosine), involved in pathways underlying band 3 protein function, have been also determined. Our results show that, in infected dogs with 1:160 IFAT titer, high MDA plasma levels and oxidation of -SH groups are associated to increased P-Tyr expression levels, leading to a reduction in anion exchange capability throughout 6 months of diagnosis. On the other hand, infected dogs with 1:540 IFAT titer, exhibited oxidative conditions associated to an impaired anion exchange capability at diagnosis, were ameliorated after 6 months. Such findings suggest that (1) band 3 protein-mediated anion transport is reduced by oxidative conditions associated to leishmaniasis, putatively via phosphorylative pathways; (2) band 3 protein efficiency may account for canine leishmaniasis development; and (3) the assessment of band 3 protein function may represent an additional tool for canine leishmaniasis diagnosis and monitoring of its development, with potential application to humans, either in case of leishmaniasis or other oxidative-related pathologies.

Keywords: Band 3 protein; Canine leishmaniasis; Erythrocytes; Oxidative stress; Phosphorylation pathways; SO4 = uptake.

MeSH terms

  • Animals
  • Anion Exchange Protein 1, Erythrocyte / metabolism*
  • Biomarkers / blood
  • Dog Diseases / blood*
  • Dogs
  • Female
  • Glutathione / blood
  • Leishmaniasis / blood*
  • Leishmaniasis / veterinary
  • Male
  • Malondialdehyde / blood
  • Oxidative Stress
  • Phosphorylation
  • Protein Processing, Post-Translational*

Substances

  • Anion Exchange Protein 1, Erythrocyte
  • Biomarkers
  • Malondialdehyde
  • Glutathione