OBJECTIVE: Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also develop anemia, as evidenced by accumulation of reticulocytes in the circulation. The objective of the current study was to delineate the mechanism underlying development of anemia in the absence of SR-BI. METHODS: Expression of important mediators of erythropoiesis, as well as key enzymes in the degradation of erythrocytes, were analyzed using real-time polymerase chain reaction in SR-BI wild-type and SR-BI knockout mice. In addition, in vivo studies were performed using biotinylated erythrocytes to determine erythrocyte survival. RESULTS: mRNA expression of TAL-1, GATA-1, FOG-1, erythropoietin receptor, and ferrochelatase, important mediators of erythropoiesis, was increased in spleens of SR-BI-deficient mice. In addition, the relative amount of early Ter119(high)CD71(high) -expressing erythroblasts was increased in SR-BI-deficient spleens. Interestingly, also expression of hemeoxygenase 1 and biliverdin reductase, enzymes involved in the degradation of erythrocytes, was increased. Furthermore, an elevated amount of conjugated bilirubin, the breakdown product of hemoglobin, was found in bile. Using biotinylated erythrocytes, we show that survival of erythrocytes was decreased in SR-BI-deficient mice. Thus, the observed increased erythropoiesis in the SR-BI-deficient mice is most likely a direct response to the reduced erythrocyte lifespan. Finally, we show that increased HDL cholesterol levels due to SR-BI deficiency induce erythrocyte cholesterol:phospholipid ratios, resulting in decreased deformability and increased osmotic fragility, thereby providing an explanation for the observed reduced lifespan. CONCLUSIONS: SR-BI is not only essential for HDL cholesterol homeostasis and atherosclerosis susceptibility, but also for maintaining normal erythrocyte lifespan.
OBJECTIVE: Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also develop anemia, as evidenced by accumulation of reticulocytes in the circulation. The objective of the current study was to delineate the mechanism underlying development of anemia in the absence of SR-BI. METHODS: Expression of important mediators of erythropoiesis, as well as key enzymes in the degradation of erythrocytes, were analyzed using real-time polymerase chain reaction in SR-BI wild-type and SR-BI knockout mice. In addition, in vivo studies were performed using biotinylated erythrocytes to determine erythrocyte survival. RESULTS: mRNA expression of TAL-1, GATA-1, FOG-1, erythropoietin receptor, and ferrochelatase, important mediators of erythropoiesis, was increased in spleens of SR-BI-deficient mice. In addition, the relative amount of early Ter119(high)CD71(high) -expressing erythroblasts was increased in SR-BI-deficient spleens. Interestingly, also expression of hemeoxygenase 1 and biliverdin reductase, enzymes involved in the degradation of erythrocytes, was increased. Furthermore, an elevated amount of conjugated bilirubin, the breakdown product of hemoglobin, was found in bile. Using biotinylated erythrocytes, we show that survival of erythrocytes was decreased in SR-BI-deficient mice. Thus, the observed increased erythropoiesis in the SR-BI-deficient mice is most likely a direct response to the reduced erythrocyte lifespan. Finally, we show that increased HDL cholesterol levels due to SR-BI deficiency induce erythrocyte cholesterol:phospholipid ratios, resulting in decreased deformability and increased osmotic fragility, thereby providing an explanation for the observed reduced lifespan. CONCLUSIONS:SR-BI is not only essential for HDL cholesterol homeostasis and atherosclerosis susceptibility, but also for maintaining normal erythrocyte lifespan.
Authors: Ayce Yesilaltay; Gregoriy A Dokshin; Dolores Busso; Li Wang; Dalia Galiani; Tony Chavarria; Eliza Vasile; Linda Quilaqueo; Juan Andrés Orellana; Dalia Walzer; Ruth Shalgi; Nava Dekel; David F Albertini; Attilio Rigotti; David C Page; Monty Krieger Journal: Proc Natl Acad Sci U S A Date: 2014-11-03 Impact factor: 11.205
Authors: Ling Guo; Zhong Zheng; Junting Ai; Deborah A Howatt; Paul R Mittelstadt; Seth Thacker; Alan Daugherty; Jonathan D Ashwell; Alan T Remaley; Xiang-An Li Journal: Arterioscler Thromb Vasc Biol Date: 2014-03-06 Impact factor: 8.311
Authors: Majda El Bouhassani; Sophie Gilibert; Martine Moreau; Flora Saint-Charles; Morgan Tréguier; Francesco Poti; M John Chapman; Wilfried Le Goff; Philippe Lesnik; Thierry Huby Journal: J Biol Chem Date: 2011-03-20 Impact factor: 5.157
Authors: Allison L McDaniel; Heather M Alger; Janet K Sawyer; Kathryn L Kelley; Nancy D Kock; J Mark Brown; Ryan E Temel; Lawrence L Rudel Journal: Am J Pathol Date: 2013-02-01 Impact factor: 4.307