Sulphydryl modifications alter scramblase activity in murine sickle cell disease

British Journal of Haematology
K de Jong, Frans A Kuypers

Abstract

Increased oxidant stress has been suggested to play a role in the process of phosphatidylserine (PS) externalization in the red blood cells of sickle cell patients. Inhibition of the ATP-driven translocation from outer to inner monolayer (flippase) by sulphydryl modification has been established. The present study showed that phospholipid scrambling was also sensitive to protein sulphydryl modification. Treatment with N-ethylmaleimide lead to enhanced PS exposure and a lower Ca(++) requirement for scrambling. In contrast, pyridyldithioethylamine treatment inhibited PS exposure. Red blood cells from a murine model for sickle cell disease exhibited a reduced response to both reagents, suggestive of previous sulphydryl modifications to the protein(s) involved in phospholipid scrambling. We conclude that sulphydryl modifications to both scramblase and flippase underlie the enhanced formation of PS-exposing cells in sickle cell disease.

References

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Citations

Apr 13, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Won-Hee JangJin-Ho Chung
Apr 9, 2008·Current Opinion in Hematology·David L Daleke
Nov 21, 2007·Hematology·Frans A Kuypers
Nov 21, 2007·Hematology·Kenneth I Ataga, Nigel S Key
Mar 23, 2010·FEBS Letters·Edouard M Bevers, Patrick L Williamson
Mar 5, 2014·Hematology/oncology Clinics of North America·Frans A Kuypers
Jun 30, 2009·Toxicon : Official Journal of the International Society on Toxinology·Gloria CeledónCarlos Alvarez
Jun 25, 2009·British Journal of Haematology·Latorya A BarberRobert S Franco
Mar 18, 2008·British Journal of Haematology·Ward Hagar, Elliott Vichinsky
Jul 4, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Keunyoung KimJin-Ho Chung
Mar 14, 2013·Blood Cells, Molecules & Diseases·Boris E ShmuklerSeth L Alper
Jun 26, 2018·British Journal of Haematology·Anke HannemannJohn S Gibson
Feb 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Ji-Yoon NohJin-Ho Chung
May 8, 2007·Archives of Biochemistry and Biophysics·Santosh Kumar SahuGopala Krishna Aradhyam

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