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.
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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
Lambeth,JD
中科院分区:
生物学3区
文献类型:
--
作者:
Wilson,E;Rice,WG;KinkadeJr,JM;MerrillJr,AH;Arnold,RR;Lambeth,JD

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鞘氨醇长链碱基(二氢鞘氨醇和鞘氨醇)最近被证明可以在体外抑制蛋白激酶 C [Y. Hannunet al.(1986)J。生物。 Chem.261, 12604–12609] 和完整的人中性粒细胞中,它们阻止超氧化物生成呼吸爆发的激活 [E. Wilsonet al.(1986)J。生物。化学261, 12616–12623]。在本研究中,我们使用鞘氨醇来研究激动剂诱导的中性粒细胞颗粒内容物分泌的途径。各种激动剂[佛波醇12-肉豆蔻酸-13-乙酸酯(PMA)、甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸(fMLP)和钙离子载体A23187]诱导的特定颗粒成分乳铁蛋白的分泌被鞘氨醇完全抑制,ED50为6至10μm。 PMA 诱导的溶菌酶分泌(存在于天青颗粒和特异性颗粒中)被完全阻断,ED50 为 10 μm,而 fMLP 诱导的分泌仅被抑制约 50%。嗜天青颗粒蛋白β-葡萄糖醛酸酶和髓过氧化物酶的分泌被fMLP和A23187激活,但不被PMA激活,并且不受鞘氨醇影响。在存在鞘氨醇的情况下使用 A23187 可以区分蛋白激酶 C 依赖性途径和非依赖性途径的钙激活。鞘氨醇的作用不是通过中和细胞内酸性区室介导的,因为用抑制浓度的鞘氨醇处理中性粒细胞不会显着改变标记甲胺的摄取。我们得出结论,至少有两种机制分别参与特异性颗粒和嗜天青颗粒分泌的调节:蛋白激酶C依赖性途径和不涉及蛋白激酶C的钙依赖性途径。
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.
DOI: --
发表时间: 1979
影响因子: 6
作者:
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通讯作者: J. Oliver
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发表时间: 1981
期刊:
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作者:
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发表时间: 1982-07
期刊: The Journal of biological chemistry
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作者:
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人单核细胞中过氧化物酶的表征和定量。
DOI: --
发表时间: 1978
期刊: Biochimica et Biophysica Acta
影响因子: --
作者:
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Ca2 和磷脂依赖性蛋白激酶(蛋白激酶 C)活性并不是人类中性粒细胞分泌所必需的。
DOI: --
发表时间: 1986
期刊: Blood
影响因子: 20.3
作者:
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通讯作者: Boxer,LA