Sodium salicylate promotes neutrophil apoptosis by stimulating caspase-dependent turnover of Mcl-1
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Tarih
2006
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
American Association of Immunologists
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mcl-1 is an antiapoptotic member of the Bcl-2 family of proteins that plays a central role in cell survival of neutrophils and other cells. The protein is unusual among family members in that it has a very short half-life of 2-3 h. In this report, we show that sodium salicylate (at 10 mM) greatly enhances the rate at which neutrophils undergo apoptosis and, in parallel, greatly accelerates the turnover rate of Mcl-1, decreasing its half-life to only 90 min. Whereas constitutive and GM-CSF-modified Mcl-1 turnover is regulated by the proteasome, the accelerated sodium salicylate-induced Mcl-1 turnover is mediated largely via caspases. Sodium salicylate resulted in rapid activation of caspase-3, -8, -9, and -10, and salicylate-accelerated Mcl-1 turnover was partly blocked by caspase inhibitors. Sodium salicylate also induced dramatic changes in the activities of members of the MAPIC family implicated in Mcl-1 turnover and apoptosis. For example, sodium salicylate blocked GM-CSF-stimulated Erk and Akt activation, but resulted in rapid and sustained activation of p38-MAPK, an event mimicked by okadaic acid that also accelerates Mcl-1 turnover and neutrophil apoptosis. These data thus shed important new insights into the dynamic and highly regulated control of neutrophil apoptosis that is effected by modification in the rate of Mcl-1 turnover. Copyright © 2006 by The American Association of Immunologists, Inc.
Açıklama
Anahtar Kelimeler
caspase; caspase 10; caspase 3; caspase 8; caspase 9; caspase inhibitor; granulocyte macrophage colony stimulating factor; mitogen activated protein kinase; mitogen activated protein kinase p38; okadaic acid; proteasome; protein bcl 2; protein kinase B; protein mcl 1; salicylate sodium; apoptosis; article; cell survival; controlled study; enzyme activation; human; human cell; neutrophil; priority journal; protein family; protein metabolism
Kaynak
Journal of Immunology
WoS Q Değeri
Scopus Q Değeri
Q2
Cilt
176
Sayı
2
