Cloned T-cell proliferation and synthesis of specific proteins are inhibited by quinine.

Cloned T-cell proliferation and synthesis of specific proteins are inhibited by quinine.
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奎宁可抑制克隆 T 细胞的增殖和特定蛋白质的合成。

DOI:
10.1073/pnas.83.13.4739
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发表时间:
1986
影响因子:
11.1
通讯作者:
Prystowsky,MB
Prystowsky,MB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sabath,DE;Monos,DS;Lee,SC;Deutsch,C;Prystowsky,MB

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重组人白细胞介素2 (il -2)驱动克隆小鼠t辅助细胞系L2的增殖。初始G1激活发生在刺激后的第一个20小时,DNA合成(S期)在rIL-2刺激后大约20小时开始。在G1激活期间观察到三种蛋白质合成模式。I型蛋白(如p72和p66)早在刺激后4小时就以接近最大的速率合成,通过G1到S相转变的合成速率几乎没有变化。II型蛋白(如p52和p36)在刺激后早期可检测到,但它们的合成速度在G1激活过程中继续增加,在刺激后24-28小时达到最大。III型蛋白(如p93、p89和p63)在rIL-2刺激后4或8小时合成最多,然后它们的合成速率明显下降到刺激前的水平。II型蛋白,p52和p36,被证明与细胞增殖相关,因为它们的合成速率在L2细胞增殖时最大,当细胞恢复到静止状态时下降。钾通道阻滞剂奎宁在il -2刺激后0或2小时对细胞生长和p52和p36的合成有抑制作用,而在il -2刺激后6小时无抑制作用。因此,在il -2刺激后2 - 6小时,L2细胞中发生的奎宁敏感事件对于II型蛋白的合成、DNA合成和细胞增殖是必要的。
Recombinant human interleukin 2 (rIL-2) drives the proliferation of the cloned murine T-helper line L2. The initial G1 activation occurs during the first 20 hr after stimulation, with DNA synthesis (S phase) beginning approximately 20 hr after rIL-2 stimulation. Three patterns of protein synthesis were observed during G1 activation. Type I proteins (e.g., p72 and p66) were synthesized at near maximal rates as early as 4 hr after stimulation, with little change in rates of synthesis through the G1 to S phase transition. Type II proteins (e.g., p52 and p36) were detectable early after stimulation, but their rates of synthesis continued to increase throughout G1 activation, becoming maximal 24-28 hr after stimulation. Type III proteins (e.g., p93, p89, and p63) were synthesized maximally 4 or 8 hr after rIL-2 stimulation, then their rates of synthesis declined markedly to prestimulation levels. Type II proteins, p52 and p36, were shown to be correlated with cell proliferation, since their rates of synthesis were maximal while L2 cells were proliferating and declined as the cells returned to a quiescent state. The potassium channel blocker quinine inhibited cell growth and the synthesis of p52 and p36 when added 0 or 2 hr after rIL-2 stimulation but not when added 6 hr after rIL-2 stimulation. Thus, a quinine-sensitive event occurring in L2 cells between 2 and 6 hr after rIL-2 stimulation is necessary for synthesis of type II proteins, DNA synthesis, and cell proliferation.