Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

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TitleVisualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography
Publication TypeJournal Article
Year of Publication2016
AuthorsDarrow MC, Zhang Y, Cinquin BP, Smith EA, Boudreau R, Rochat RH, Schmid MF, Xia Y, Larabell CA, Chiu W
Journal TitleJ Cell Sci
Volume129
Pages3511-7
Journal DateSep 15
ISBN Number1477-9137 (Electronic)0021-9533 (Linking)
Accession Number27505892
KeywordsCryogenic soft X-ray tomography, Red blood cell, Red cell morphology, Sickle cell disease, Sphingosine kinase inhibitor
Abstract

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of the sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/27505892http://jcs.biologists.org/content/129/18/3511.long