Rac and p38 kinase mediate 5-lipoxygenase translocation and cell death.
Rac and p38 kinase mediate 5-lipoxygenase translocation and cell death.
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Rac 和 p38 激酶介导 5-脂氧合酶易位和细胞死亡。
DOI：
10.1006/bbrc.2001.4937
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发表时间：
2001
影响因子：
3.1
通讯作者：
J. Kim
中科院分区：
文献类型：
--
作者：
Y. Eom;S. H. Cho;J. S. Hwang;S. B. Yoon;D. Na;I. Kang;S. S. Kang;W. K. Song;J. Kim
5-脂氧合酶（5-LO）是花生四烯酸合成白三烯的关键酶，其激活后通常转移至核膜。虽然Ca（2+）是5-LO转运的重要因素，但其转运机制的细节还不清楚。在这里，我们表明离子霉素，钙（2+）离子载体，诱导5-LO易位和坏死的细胞死亡在大鼠-2成纤维细胞，表明5-LO的激活和细胞死亡之间的潜在关系。在表达显性负Rac 1突变体的Rat 2-Rac（N17）细胞中，这些作用明显减弱。p38 MAP激酶特异性抑制剂SB 203580或Ca（2+）螯合剂EGTA预处理同样减少了离子霉素诱导的5-LO易位和细胞死亡，但MEK抑制剂PD 98059没有。因此，Rac和p38 MAP激酶似乎是导致Rat-2成纤维细胞中5-LO易位和坏死细胞死亡的Ca（2+）依赖性途径中的组分。
5-Lipoxygenase (5-LO) is a key enzyme involved in the synthesis of leukotrienes from arachidonic acid, and its activation is usually followed by translocation to the nuclear envelope. The details of mechanisms involved in the translocation of 5-LO are not well understood, though Ca(2+) is known to be essential. Here we show that ionomycin, a Ca(2+) ionophore, induces 5-LO translocation and necrotic cell death in Rat-2 fibroblasts, suggesting a potential relationship between activation of 5-LO and cell death. These effects were markedly attenuated in Rat2-Rac(N17) cells expressing a dominant negative Rac1 mutant. Pretreatment with SB203580, a specific inhibitor of p38 MAP kinase, or EGTA, a Ca(2+) chelator, likewise diminished ionomycin-induced 5-LO translocation and cell death, but PD98059, a MEK inhibitor, did not. Thus, Rac and p38 MAP kinase appear to be components in a Ca(2+)-dependent pathway leading to 5-LO translocation and necrotic cell death in Rat-2 fibroblasts.
DOI：
10.1172/jci117889
发表时间：
1995-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
John W Woods;Michael J. Coffey;T. Brock;Irwin I. Singer;Marc Peters-Golden
通讯作者：
John W Woods;Michael J. Coffey;T. Brock;Irwin I. Singer;Marc Peters-Golden