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Published on: September 28, 2019
Sphingosine-1-phosphate Decreases Erythrocyte Dysfunction Induced by β-Amyloid
Francesco Misiti1, Pierluigi Diotaiuti1, Giovanni Enrico Lombardo2
1Human Sciences, Social and Health Department, University of Cassino and Lazio Meridionale, V. S. Angelo, Loc. Folcara, 03043 Cassino, Italy.
Abstract:
Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer's disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show red blood cell (RBC) membrane-binding capacity and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Ab-treated RBCs. In RBCs following different treatments, the ATP, 2,3 DPG and cAMP levels and caspase 3 activity were determined by spectrophotometric and immunoassay. S1P rescued the inhibition of ATP release from RBCs triggered by Ab, through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.
Insights
Sphingosine-1-phosphate (S1P) protects red blood cells from amyloid beta (Aβ) damage in Alzheimer's disease. S1P restores ATP release and oxygen delivery, offering new therapeutic potential for AD.
Area of Science:
- Neuroscience
- Biochemistry
- Hematology
Background:
- Amyloid beta (Aβ) peptides are key in Alzheimer's disease (AD) pathogenesis.
- Soluble Aβ oligomers impair red blood cell (RBC) function and oxygen delivery.
- Bioactive lipids are explored for protection against Aβ toxicity.
Purpose of the Study:
- Investigate sphingosine-1-phosphate (S1P) role in ATP release in Aβ-treated RBCs.
- Elucidate S1P's protective mechanism against Aβ-induced RBC dysfunction.
- Explore S1P as a potential therapeutic agent for AD.
Main Methods:
- Spectrophotometric and immunoassay techniques used.
- Quantified ATP, 2,3 DPG, and cAMP levels in RBCs.
- Assessed caspase-3 activity in treated RBCs.
Main Results:
- Aβ inhibited ATP release from RBCs.
- S1P treatment rescued the inhibition of ATP release.
- S1P restored 2,3 DPG and cAMP levels and involved caspase-3.
- S1P mitigated Aβ-induced RBC functional impairments.
Conclusions:
- S1P protects RBCs against Aβ toxicity via specific molecular pathways.
- S1P normalizes ATP release and intracellular signaling in affected RBCs.
- Findings suggest S1P as a novel therapeutic strategy for Alzheimer's disease.
