p38MAPK is involved in apoptosis development in apheresis platelet concentrates after riboflavin and ultraviolet light treatment.
Transfusion
; 55(4): 848-57, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25385501
ABSTRACT
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 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 ANDMETHODS:
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 Bax, Bak, 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 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).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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Riboflavina
/
Raios Ultravioleta
/
Plaquetas
/
Fármacos Fotossensibilizantes
/
Apoptose
/
Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article