The proteome of sickle cell disease: insights from exploratory proteomic profiling

Yuditskaya, Susan; Suffredini, Anthony F.; Kato, Gregory J.

doi:10.1586/epr.10.88

Cited by 23 publications

(30 citation statements)

References 98 publications

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“…71 An altered apolipoprotein profile was identified by mass spectrometry analysis in sickle patients with pulmonary hypertension. 14,15 Sickle patients had lower ApoA-I and higher SAA levels than normal, but the PAH patients had lower and higher levels, respectively, than the sickle population as a group. Those findings provide more evidence of HDL dysfunction in the vasculopathy of SCD.…”

Section: Discussionmentioning

confidence: 84%

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Soupène¹,

Borja²,

Borda³

et al. 2016

Exp Biol Med (Maywood)

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In sickle cell disease (SCD) cholesterol metabolism appears dysfunctional as evidenced by abnormal plasma cholesterol content in a subpopulation of SCD patients. Specific activity of the high density lipoprotein (HDL)-bound lecithin cholesterol acyltransferase (LCAT) enzyme, which catalyzes esterification of cholesterol, and generates lysoPC (LPC) was significantly lower in sickle plasma compared to normal. Inhibitory amounts of LPC were present in sickle plasma, and the red blood cell (RBC) lysophosphatidylcholine acyltransferase (LPCAT), essential for the removal of LPC, displayed a broad range of activity. The functionality of sickle HDL appeared to be altered as evidenced by a decreased HDL-Apolipoprotein A-I exchange in sickle plasma as compared to control. Increased levels of oxidized proteins including ApoA-I were detected in sickle plasma. In vitro incubation of sickle plasma with washed erythrocytes affected the ApoA-I-exchange supporting the view that the RBC blood compartment can affect cholesterol metabolism in plasma. HDL functionality appeared to decrease during acute vaso-occlusive episodes in sickle patients and was associated with an increase of secretory PLA 2 , a marker for increased inflammation. Simvastatin treatment to improve the anti-inflammatory function of HDL did not ameliorate HDL-ApoA-I exchange in sickle patients. Thus, the cumulative effect of an inflammatory and highly oxidative environment in sickle blood contributes to a decrease in cholesterol esterification and HDL function, related to hypocholesterolemia in SCD.

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Section: Discussionmentioning

confidence: 84%

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Soupène¹,

Borja²,

Borda³

et al. 2016

Exp Biol Med (Maywood)

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“…The clinical value of more obscure biomarkers needs to be assessed in prospective clinical trials with the hope that some might be identified that are specific, independent indicators of future risks. Although there are legions of biomarkers already described in SCD, developing techniques, such as proteomics, may lead to the discovery of more useful molecules (Yuditskaya et al , 2010). To some extent, the value of better prognostic biomarkers is limited until more specific and effective treatments are available.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers in sickle cell disease

2011

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More than 100 different blood and urine biomarkers have been described in sickle cell disease (SCD), with the number increasing rapidly as analytical techniques develop. Nearly all of these biomarkers are abnormal in the steady state, and become more so during complications. The range of abnormalities demonstrates the multisystem nature of SCD and the complex pathophysiology. Some biomarkers indicate damage to specific organs, such as urine albumin:creatinine ratio in nephropathy, whereas others indicate more systemic processes. Biomarkers have been useful in identifying various interrelated pathological mechanisms, including haemolysis, inflammation, hypercoagulability, oxidative stress, reperfusion injury, vasculopathy and endothelial dysfunction. However, most biomarkers correlate closely with other more routine measurements, and also with each other. It is not clear that any provide specific prognostic or clinical information beyond that given by the simple measurement of haemoglobin concentration. The identification of prognostically validated biomarkers in prospective clinical trials would be useful.

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“…On the other hand, proteins associated with cellular adhesion such as Emp1 and β 1 integrins are sorted toward the pyrenocyte ( 48 ). Although it is currently unclear how this sorting process works, it is hypothesized that cytoskeletal interactions play an important role since protein sorting is defective in disorders such as elliptocytosis, spherocytosis, and sickle cell disease ( 51 , 52 ). It is clear, however, that during terminal maturation, proteins in the RBC membrane undergo dramatic reorganization.…”

Section: Macrophages Support Terminal Differentiation In Erythropoiesmentioning

confidence: 99%

From the Cradle to the Grave: The Role of Macrophages in Erythropoiesis and Erythrophagocytosis

et al. 2017

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Erythropoiesis is a highly regulated process where sequential events ensure the proper differentiation of hematopoietic stem cells into, ultimately, red blood cells (RBCs). Macrophages in the bone marrow play an important role in hematopoiesis by providing signals that induce differentiation and proliferation of the earliest committed erythroid progenitors. Subsequent differentiation toward the erythroblast stage is accompanied by the formation of so-called erythroblastic islands where a central macrophage provides further cues to induce erythroblast differentiation, expansion, and hemoglobinization. Finally, erythroblasts extrude their nuclei that are phagocytosed by macrophages whereas the reticulocytes are released into the circulation. While in circulation, RBCs slowly accumulate damage that is repaired by macrophages of the spleen. Finally, after 120 days of circulation, senescent RBCs are removed from the circulation by splenic and liver macrophages. Macrophages are thus important for RBCs throughout their lifespan. Finally, in a range of diseases, the delicate interplay between macrophages and both developing and mature RBCs is disturbed. Here, we review the current knowledge on the contribution of macrophages to erythropoiesis and erythrophagocytosis in health and disease.

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The proteome of sickle cell disease: insights from exploratory proteomic profiling

Cited by 23 publications

References 98 publications

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Biomarkers in sickle cell disease

From the Cradle to the Grave: The Role of Macrophages in Erythropoiesis and Erythrophagocytosis

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