期刊
CELLS
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cells11071250
关键词
red blood cell deformability; capillary transit; shear stress; phosphorylation; cytoskeletal proteins
类别
资金
- Turkish Scientific and Technical Council [SBAG-214S186]
This study investigates the role of the cAMP signaling mechanism in modulating shear-induced red blood cell (RBC) deformability and examines changes in the phosphorylation of the RBC proteome. The inhibition of signaling molecules significantly deteriorates shear-induced RBC deformability. The cAMP/PKA pathway regulates RBC deformability by triggering significant alterations in the phosphorylation state of RBCs.
Red blood cell (RBC) deformability is modulated by the phosphorylation status of the cytoskeletal proteins that regulate the interactions of integral transmembrane complexes. Proteomic studies have revealed that receptor-related signaling molecules and regulatory proteins involved in signaling cascades are present in RBCs. In this study, we investigated the roles of the cAMP signaling mechanism in modulating shear-induced RBC deformability and examined changes in the phosphorylation of the RBC proteome. We implemented the inhibitors of adenylyl cyclase (SQ22536), protein kinase A (H89), and phosphodiesterase (PDE) (pentoxifylline) to whole blood samples, applied 5 Pa shear stress (SS) for 300 s with a capillary tubing system, and evaluated RBC deformability using a LORRCA MaxSis. The inhibition of signaling molecules significantly deteriorated shear-induced RBC deformability (p < 0.05). Capillary SS slightly increased the phosphorylation of RBC cytoskeletal proteins. Tyrosine phosphorylation was significantly elevated by the modulation of the cAMP/PKA pathway (p < 0.05), while serine phosphorylation significantly decreased as a result of the inhibition of PDE (p < 0.05). AC is the core element of this signaling pathway, and PDE works as a negative feedback mechanism that could have potential roles in SS-induced RBC deformability. The cAMP/PKA pathway could regulate RBC deformability during capillary transit by triggering significant alterations in the phosphorylation state of RBCs.
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