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Review
. 2010 Dec;7(6):833-48.
doi: 10.1586/epr.10.88.

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

Susan Yuditskaya  1 , Anthony F Suffredini, Gregory J Kato
Affiliations
Review

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

Susan Yuditskaya et al. Expert Rev Proteomics. 2010 Dec.

Abstract

The expanding realm of exploratory proteomics has added a unique dimension to the study of the complex pathophysiology involved in sickle cell disease. A review of proteomic studies published on sickle cell erythrocytes and plasma shows trends of upregulation of antioxidant proteins, an increase in cytoskeletal defects, an increase in protein repair and turnover components, a decrease in lipid raft proteins and apolipoprotein dysregulation. Many of these findings are consistent with the pathophysiology of sickle cell disease, including high oxidant burden, resulting in damage to cytoskeletal and other proteins, and erythrocyte rigidity. More unexpected findings, such as a decrease in lipid raft components and apolipoprotein dysregulation, offer previously unexplored targets for future investigation and potential therapeutic intervention. Exploratory proteomic profiling is a valuable source of hypothesis generation for the cellular and molecular pathophysiology of sickle cell disease.

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Conflict of interest statement

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1. Representative 2D fluorescence difference gel electrophoresis image from sickle cell membrane proteomics study
Two different fluorescent dyes were used – Cy3 for normal healthy controls and Cy5 for sickle cell patients. The above image is the Cy3 image of the gel, showing spots from normal healthy control samples. Spots outlined in red represent spots that were decreased in sickle cell disease; those that were increased in sickle cell disease are outlined in blue. Reproduced with permission from [43].
Figure 2
Figure 2. Representative SELDI-TOF MS spectra from plasma from patients with sickle cell disease with and without pulmonary hypertension
The vertical axes represent intensity of peaks in arbitrary units, and the horizontal axes represent mass:charge ratio (m/z). These four spectra were obtained from plasma eluted from anion exchange resin, bound to IMAC30–Cu2+ matrix, and ionized by SELDI-TOF MS. Two specimens are from sickle cell disease (SCD) patients without pulmonary arterial hypertension (A & B) and two are from SCD patients with PAH (C & D). A peak at m/z 28.1 kDa was observed at lower average intensity in SCD patients with PAH (arrows). IMAC: Immobilized metal-affinity capture; PAH: Pulmonary arterial hypertension. Reproduced with permission from [56].
Figure 3
Figure 3. Summary of major categories of erythrocyte and plasma proteins altered in sickle cell disease as identified by exploratory proteomic profiling
ApoA-I: Apolipoprotein A-I; MDA: Malondialdehyde; NO: Nitric oxide; RBC: Red blood cell; ROS: Reactive oxygen species; SAA: Serum amyloid A.
Figure 4
Figure 4. Physiologic and biochemical consequences of sickle hemoglobin polymerization-associated oxidant stress and hemolysis as a common pathway leading to alterations within the major protein biomarker categories
TCP: T-complex protein.
See this image and copyright information in PMC

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