p38MAPK is involved in apoptosis development in apheresis platelet concentrates after riboflavin and ultraviolet light treatment

Abstract

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.

p38 mitogen‐activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin‐ and ultraviolet light–treated apheresis platelet concentrates

“…15,25 In this study, we further show that this compound inhibits the mitochondrial translocation of Bax and Bid in RF/UVtreated PLTs and protects mitochondrial integrity by decreasing cyto c release and loss of DW m , effects that might explain the reduced PS exposure and caspase activities we previously reported when this inhibitor was used. 25 Although intensive investigations have reported that p38 signaling plays a critical role in modulating cell activities by either promoting apoptosis or enhancing cell survival, 22 its function in PLT apoptosis remains unclear.Rukoyatkina and coworkers 35 showed that p38 is involved in PLT apoptosis using a BH3 mimic compound ABT-737. p38 signaling is also involved in PLT apoptosis triggered by staurosporine, a microbial alkaloid, showing that inhibition of p38 decreases the loss of DW m and PS exposure.…”

“…1 Previously, we and others have demonstrated that inhibition of the stress kinase p38 improves PLT in vitro quality with or without RF/UV treatment during storage, showing a deceleration of apoptosis development. 15,25,29 Here we provide further insights into the mechanism of the impact of RF/UV treatment on PLT mitochondrial function and demonstrate that some of these activities are also modulated by p38 MAPK. Accumulating evidence demonstrates that PI-treated PLTs share highly similar behaviors with PLTs stimulated by physiologic activators, including PLT activation, degranulation, and development of apoptosis, leading to the conclusion that these processes have the same signaling mechanism.…”

“…1 These treatments aim to target the replication and/or proliferation mechanism of pathogens and to destroy residual white blood cells (WBCs) to improve the safety of blood 14,15,25 The aim of this study was to evaluate the effects of RF/UV treatment on PLT mitochondrial function and signaling, including the recently discovered release of MT by PLTs, and to determine whether p38 is involved in the modulation of these mechanisms.…”

“…Our previous studies have shown that RF/UV treatment triggers immediate phosphorylation of p38 in apheresis PCs with an increasing trend during storage. 15,25 Addition of the p38 inhibitor SB203580 before RF/UV treatment results in significantly improved ex vivo PLT quality, demonstrated by the down regulation of PLT activation, PS exposure, and apoptosis development. 15,25 In this study, we further show that this compound inhibits the mitochondrial translocation of Bax and Bid in RF/UVtreated PLTs and protects mitochondrial integrity by decreasing cyto c release and loss of DW m , effects that might explain the reduced PS exposure and caspase activities we previously reported when this inhibitor was used.…”

“…Inhibition of p38 activity before the PI treatment significantly improved the PLT quality and reduced PLT apoptosis development by the decrease of PS exposure, proapoptotic protein expression, and caspase activation. 14,15,25 The aim of this study was to evaluate the effects of RF/UV treatment on PLT mitochondrial function and signaling, including the recently discovered release of MT by PLTs, and to determine whether p38 is involved in the modulation of these mechanisms.…”