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p38MAPK is involved in apoptosis development in apheresis platelet concentrates after riboflavin and ultraviolet light treatment
Author(s) -
Chen Zhongming,
Schubert Peter,
Culibrk Brankica,
Devine Dana V.
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12905
Subject(s) - apoptosis , flow cytometry , phosphatidylserine , kinase , riboflavin , in vitro , pi , chemistry , phosphorylation , apheresis , platelet , protein kinase a , caspase 3 , microbiology and biotechnology , biology , biochemistry , immunology , programmed cell death , phospholipid , membrane
Background Pathogen inactivation ( PI ) accelerates the platelet ( PLT ) storage lesion, including apoptotic‐like changes. Proteomic studies have shown that phosphorylation levels of several kinases increase in PLT s after riboflavin and UV light ( RF ‐ PI ) treatment. Inhibition of p38MAPK improved in vitro PLT quality, but the biochemical basis of this kinase's contribution to PLT damage requires further analysis. Study Design and Methods In a pool‐and‐split design, apheresis PLT concentrates were either treated or kept untreated with or without selected kinase inhibitors. Samples were analyzed throughout 7 days of storage, monitoring in vitro quality variables including phosphatidylserine exposure, degranulation, and glucose metabolism. Changes in the protein expression of B ax, B ak, and Bcl ‐ xL and the activities of caspase‐3 and ‐9 were determined by immunoblot analysis and flow cytometry, respectively. Results The expression levels of the proapoptotic proteins B ax and B ak, but not the antiapoptotic protein Bcl ‐ xL , were significantly increased after the RF ‐ PI treatment. This trend was reversed in the presence of p38MAPK inhibitor SB 203580. As a result of increasing proapoptotic protein levels, caspase‐3 and ‐9 activities were significantly increased in RF ‐ PI treatment during storage compared with control (p < 0.05). Similarly, p38MAPK inhibition significantly reduced these caspase activities compared with vehicle control after RF ‐ PI treatment (p < 0.05). Conclusion These findings revealed that p38MAPK is involved in signaling leading to apoptosis triggered by RF ‐ PI . Elucidation of the biochemical processes influenced by PI is a necessary step in the development of strategies to improve the PLT quality and ameliorate the negative effects of PI treatment.