Multiple apoptotic death types triggered through activation of separate pathways by cAMP and inhibitors of protein phosphatases in one (IPC leukemia) cell line.
Multiple apoptotic death types triggered through activation of separate pathways by cAMP and inhibitors of protein phosphatases in one (IPC leukemia) cell line.
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在一种（IPC 白血病）细胞系中，cAMP 和蛋白磷酸酶抑制剂激活不同的途径而引发多种细胞凋亡死亡类型。
DOI：
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发表时间：
1994
影响因子：
4
通讯作者：
Stein Ove Døskeland
中科院分区：
文献类型：
--
作者：
Bjørn Tore Gjertsen;Lill Irene Cressey;Sandrine Ruchaud;Gunnar Houge;Michel Lanotte;Stein Ove Døskeland
中等浓度的蛋白磷酸酶抑制剂冈田酸和花萼蛋白A诱导三种类型的凋亡性早幼粒细胞白血病细胞死亡，其在超微结构和多核苷酸断裂方面各不相同。较高浓度 (> 50 nM) 的 Calyculin A 可诱导具有高 ATP 和明显的微线粒体增生的非凋亡死亡类型。这表明蛋白质磷酸化途径参与了多种死亡途径的触发。 cAMP 激酶的激活诱导另一种细胞凋亡死亡类型，优先影响 S 期细胞。事实上，cAMP 通过两种方式阻止 IPC 早幼粒细胞增殖：（1）阻断 G1 晚期（阻止新细胞进入 DNA 复制）； (2)诱导S期细胞凋亡。 cAMP 和磷酸酶抑制剂通过不同的途径发挥作用。这些抑制剂可以抑制 cAMP 诱导的死亡，但浓度必须足够高，才能使细胞转向另一种不太明显的死亡类型。因此，大田酸和花萼蛋白 A 的肿瘤促进活性可能不是通过防止细胞凋亡来实现的。 DNA 片段化与有限 28 S rRNA 裂解的新特征相关，表明在某些细胞凋亡死亡类型中，协调的多核苷酸裂解可能针对非法多核苷酸。
The protein phosphatase inhibitors okadaic acid and calyculin A at moderate concentrations induced three types of apoptotic promyelocytic leukemia cell death, distinct with respect to ultrastructure and polynucleotide fragmentation. Calyculin A at higher concentrations (> 50 nM) induced a non-apoptotic death type with high ATP and pronounced micromitochondriosis. This suggests that protein phosphorylation pathways are involved in the triggering of several death pathways. Activation of the cAMP kinase induced yet another apoptotic death type, preferentially affecting cells in S-phase. In fact, cAMP acted in two ways to stop IPC promyelocyte proliferation: (1) block in late G1 (preventing new cells from entering DNA replication); and (2) induction of apoptosis in S-phase. cAMP and phosphatase inhibitors acted via distinct pathways. The inhibitors suppressed cAMP-induced death, but only at concentrations high enough to commit the cells to alternative, less conspicuous death types. The tumor-promoting activity of okadaic acid and calyculin A may therefore not be by protection against apoptosis. DNA fragmentation correlated with the novel feature of limited 28 S rRNA cleavage, suggesting co-ordinated polynucleotide cleavage, possibly directed against illegitimate polynucleotides, in some apoptotic death types.
DOI：
10.1073/pnas.89.22.11093
发表时间：
1992-11-15
影响因子：
11.1
作者：
ERIKSSON, JE;BRAUTIGAN, DL;GOLDMAN, RD
通讯作者：
GOLDMAN, RD
影响因子：
56.9
作者：
KANE, DJ;SARAFIAN, TA;BREDESEN, DE
通讯作者：
BREDESEN, DE