Comparative proteomics reveals deficiency of SLC9A1 (sodium/hydrogen exchanger NHE1) in β-adducin null red cells.

Br J Haematol 2011 Aug 21;154(4):492-501. Epub 2011 Jun 21.

Puget Sound Blood Center, Seattle, WA 98104, USA.

Spherocytosis is one of the most common inherited disorders, yet presents with a wide range of clinical severity. While several genes have been found mutated in patients with spherocytosis, the molecular basis for the variability in severity of haemolytic anaemia is not entirely understood. To identify candidate proteins involved in haemolytic anaemia pathophysiology, we utilized a label-free comparative proteomic approach to detect differences in red blood cells (RBCs) from normal and β-adducin (Add2) knock-out mice. We detected seven proteins that were decreased and 48 proteins that were increased in β-adducin null RBC ghosts. Since haemolytic anaemias are characterized by reticulocytosis, we compared reticulocyte-enriched samples from phenylhydrazine-treated mice with mature RBCs from untreated mice. Among the 48 proteins increased in Add2 knockout RBCs, only 11 were also increased in reticulocytes. Of the proteins decreased in Add2 knockout RBCs, α-adducin showed the greatest intensity difference, followed by SLC9A1, the sodium-hydrogen exchanger previously termed NHE1. We verified these mass spectrometry results by immunoblot. This is the first example of SLC9A1deficiency in haemolytic anaemia and suggests new insights into the mechanisms leading to fragile RBCs.

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http://dx.doi.org/10.1111/j.1365-2141.2011.08612.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515348PMC
August 2011
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References

(Supplied by CrossRef)
Na+/H+ exchangers and the regulation of volume
Alexander et al.
Acta Physiologica (Oxford) 2006
The removal of leukocytes and platelets from whole blood
Beutler et al.
Journal of Laboratory and Clinical Medicine 1976
Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane
Campanella et al.
Proceedings of the National Academy of Sciences of the United States of America 2005

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