Reactive oxygen species and phosphatidylserine externalization in murine sickle red cells.
Due to their role in oxygen transport and the presence of redox active haemoglobin molecules, red blood cells (RBC) generate relatively high levels of reactive oxygen species (ROS). To counteract the potential deleterious effects of ROS, RBCs have a well-integrated network of anti-oxidant mechanisms to combat this oxidative stress. ROS formation is increased in sickle-cell disease (SCD) and our studies in a murine SCD model showed a significant increase in the generation of ROS when compared with normal mice. Our data also indicated that murine sickle RBCs exhibit a significantly increased ATP catabolism, partly due to the increased activity of glucose-6-phosphate dehydrogenase and glutathione reductase to regenerate intracellular glutathione (GSH) levels to neutralize the adverse milieu of oxidative stress. Higher ATP consumption by the murine sickle RBCs, together with the increased ROS formation and impairment of the aminophospholipid translocase or flipase may underlie the exposure of phosphatidylserine on the surface of these cells.
Banerjee
Tinku
T
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Kuypers
Frans A
FA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D005980:Glutathione Reductase / Q000032:analysis; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D017382:Reactive Oxygen Species / Q000032:analysis*
D002352:Carrier Proteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione