BackgroundPathogen inactivation (PI) accelerates the platelet (PLT) storage lesion, including apoptotic‐like changes. Proteomic studies have shown that phosphorylation levels of several kinases increase in PLTs 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 MethodsIn 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 Bax, Bak, and Bcl‐xL and the activities of caspase‐3 and ‐9 were determined by immunoblot analysis and flow cytometry, respectively.ResultsThe expression levels of the proapoptotic proteins Bax and Bak, 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 SB203580. 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).ConclusionThese 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.