Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification
Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification
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DOI：
10.1073/pnas.93.2.654
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发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
Babior, BM
中科院分区：
文献类型：
--
作者：
Gottlieb, RA;Nordberg, J;Babior, BM
我们先前已经表明，在缺乏粒细胞集落刺激因子的中性粒细胞中，细胞凋亡之前是酸化的，并且粒细胞集落刺激因子赋予中性粒细胞的抗细胞凋亡的保护依赖于这种酸化的延迟。为了检验酸化可能是细胞凋亡的一般特征的假设，我们检查了另一种细胞系Jurkat细胞中的细胞内pH变化，一种T淋巴母细胞系，用抗Fas IgM、放线菌酮或暴露于短波长UV光诱导经历凋亡。我们发现酸化响应于用这些试剂的处理而发生，并且酸化先于DNA片段化。还发现Jurkat细胞具有酸性内切核酸酶，其在低于pH 6.8时有活性，与该酶在细胞凋亡过程中染色质消化中的可能作用相一致，在用抗Fas抗体或放线菌酮处理期间或在UV暴露后用咪唑或氯喹碱孵育细胞减少了细胞凋亡，如通过核形态学和DNA含量所评估的，咪唑和氯喹的碱化作用通过证明用抗Fas抗体，放线菌酮，或UV在碱的存在下减少，与在没有碱的情况下孵育的类似处理的细胞相比，我们得出结论，酸化是程序性细胞死亡的早期事件，并且可能是基因组破坏所必需的。
We have previously shown that in neutrophils deprived of granulocyte colony-stimulating factor, apoptosis is preceded by acidification and that the protection against apoptosis conferred on neutrophils by granulocyte colony-stimulating factor is dependent upon delay of this acidification, To test the hypothesis that acidification could be a general feature of apoptosis, we examined intracellular pH changes in another cell line, Jurkat cells, a T-lymphoblastoid line, were induced to undergo apoptosis with anti-Fas IgM, cycloheximide, or exposure to short-wavelength UV light, We found that acidification occurred in response to treatment with these agents and that acidification preceded DNA fragmentation, Jurkat cells were also found to possess an acid endonuclease that is active below pH 6.8, compatible with a possible role for this enzyme in chromatin digestion during apoptosis, Incubation of the cells with the bases imidazole or chloroquine during treatment with anti Fas antibody or cycloheximide or after UV exposure decreased apoptosis as assessed by nuclear morphology and DNA content, The alkalinizing effect of imidazole and chloroquine was shown by the demonstration that the percentage of cells with an intracellular pH below 6.8 after treatment with anti-Fas antibody, cycloheximide, or UV was diminished in the presence of base as compared with similarly treated cells incubated in the absence of base, We conclude that acidification is an early event in programmed cell death and may be essential for genome destruction.