|
|
Blood, 15 August 2005, Vol. 106, No. 4, pp. 1454-1459.
Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2005-01-0368.
 Previous Article | Next Article 
Submitted January 26, 2005
Accepted April 14, 2005
Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis
Lucia De Franceschi, Alicia Rivera, Mark D Fleming, Marek Honczarenko, Luanne L Peters, Philippe Gascard, Narla Mohandas, and Carlo Brugnara*
Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy
Department of Laboratory Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
The Jackson Laboratory, Bar Harbor, ME, USA
New York Blood Center, New York, NY, USA
* Corresponding author; email: carlo.brugnara{at}childrens.harvard.edu.
Mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis), and decreased membrane stability (Shi TS et al., J. Clin. Invest. 103:331,1999). Here, we have characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared to wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75±1.06 vs. 6.08±0.09 mmol/L cell x min, p < 0.04) and a decrease in Km (1.01±0.06 vs.1.47±1.02 µM, p < 0.03), indicating an increased sensitivity to activation by intracellular Ca. The in vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker: Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival, and increased number of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/-, and band 3 -/+ mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, K and water loss via the Gardos channel may play an important protective role in compensating for the reduced surface membrane area of HS erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
From Budapest to Bar Harbor
- James S. Wiley
Blood 2005 106: 1145-1146.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Iolascon, L. De Falco, F. Borgese, M. R. Esposito, R. A. Avvisati, P. Izzo, C. Piscopo, H. Guizouarn, A. Biondani, A. Pantaleo, et al.
A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis
Haematologica,
August 1, 2009;
94(8):
1049 - 1059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Pasini, M. Kirkegaard, D. Salerno, P. Mortensen, M. Mann, and A. W. Thomas
Deep Coverage Mouse Red Blood Cell Proteome: A First Comparison with the Human Red Blood Cell
Mol. Cell. Proteomics,
July 1, 2008;
7(7):
1317 - 1330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rivera, L. De Franceschi, L. L. Peters, P. Gascard, N. Mohandas, and C. Brugnara
Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes
Am J Physiol Cell Physiol,
November 1, 2006;
291(5):
C880 - C886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
