Protein kinase C inhibition by sphingoid long-chain bases: effects on secretion in human neutrophils.
Protein kinase C inhibition by sphingoid long-chain bases: effects on secretion in human neutrophils.
复制标题
鞘氨醇长链碱基对蛋白激酶 C 的抑制:对人中性粒细胞分泌的影响。
DOI:
10.1016/0003-9861(87)90487-5
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发表时间:
1987
影响因子:
3.9
通讯作者:
Lambeth,JD
中科院分区:
文献类型:
--
作者:
Wilson,E;Rice,WG;KinkadeJr,JM;MerrillJr,AH;Arnold,RR;Lambeth,JD
Sphingoid long-chain bases (sphinganine and sphingosine) have recently been shown to inhibit protein kinase C bothin vitro[Y. Hannunet al.(1986)J. Biol. Chem.261, 12604–12609] and in intact human neutrophils, in which they block activation of the superoxide-generating respiratory burst [E. Wilsonet al.(1986)J. Biol. Chem.261, 12616–12623]. In the present study we have used sphingosine to investigate the pathways for agonist-induced secretion of neutrophil granule contents. Induction of secretion of the specific granule component lactoferrin by a variety of agonists [phorbol 12-myristate-13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore A23187] was completely inhibited by sphingosine with an ED50of 6 to 10 μm. PMA-induced secretion of lysozyme (present in both the azurophilic and specific granules) was completely blocked with an ED50of 10 μm, whereas fMLP-induced secretion was only about 50% inhibited. Secretion of the azurophilic granule proteins β-glucuronidase and myeloperoxidase was activated by fMLP and A23187, but not by PMA, and was not affected by sphingosine. The use of A23187 in the presence of sphingosine allowed differentiation between calcium activation of protein kinase C-dependent versus -independent pathways. The effect of sphingosine was not mediated by neutralizing intracellular acidic compartments, since treatment of neutrophils with inhibitory concentrations of sphingosine did not significantly alter the uptake of labeled methylamine. We conclude that at least two mechanisms participate in the regulation of specific and azurophilic granule secretion, respectively: a protein kinase C-dependent pathway and a calcium-dependent pathway which does not involve protein kinase C.
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影响因子:
6
作者:
E. Becker;M. Sigman;J. Oliver
通讯作者:
J. Oliver
DOI:
--
发表时间:
1981
期刊:
影响因子:
--
作者:
J. Smolen;H. Korchak;G. Weissmann
通讯作者:
G. Weissmann
DOI:
10.1016/s0021-9258(18)34459-4
发表时间:
1982-07
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
M. Castagna;Y. Takai;K. Kaibuchi;K. Sano;U. Kikkawa;Y. Nishizuka
通讯作者:
M. Castagna;Y. Takai;K. Kaibuchi;K. Sano;U. Kikkawa;Y. Nishizuka
DOI:
--
发表时间:
1978
期刊:
Biochimica et Biophysica Acta
影响因子:
--
作者:
A. Bos;R. Wever;D. Roos
通讯作者:
D. Roos
影响因子:
20.3
作者:
Balazovich,KJ;Smolen,JE;Boxer,LA
通讯作者:
Boxer,LA