Premium
Cyclic AMP delays neutrophil apoptosis via stabilization of Mcl‐1
Author(s) -
Kato Takayuki,
Kutsuna Haruo,
Oshitani Nobuhide,
Kitagawa Seiichi
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.07.034
Subject(s) - cycloheximide , lactacystin , proteasome , apoptosis , mg132 , survivin , proteasome inhibitor , chemistry , microbiology and biotechnology , biology , biochemistry , protein biosynthesis
Human neutrophils underwent spontaneous apoptosis, which was accompanied by degradation of Mcl‐1, but not other anti‐apoptotic molecules (cIAP1, cIAP2, A1, survivin and Bcl‐2). Spontaneous neutrophil apoptosis and Mcl‐1 degradation were prevented by cyclic AMP (cAMP) agonists (dibutyryl cAMP and prostaglandin E 1 ), and the effects of cAMP agonists on neutrophils were highly resistant to cycloheximide, a protein synthesis inhibitor, although slight increase in Mcl‐1 mRNA expression was induced by cAMP agonists. Proteasome inhibitors (epoxomicin and lactacystin) also prevented spontaneous neutrophil apoptosis and Mcl‐1 degradation to the same extent as cAMP agonists, and no additive effect was obtained by combination of cAMP agonists and proteasome inhibitors. These findings suggest that cAMP agonists, like proteasome inhibitors, delay neutrophil apoptosis primarily via stabilization of Mcl‐1.