INTRACELLULAR CA2+ POOL CONTENT IS LINKED TO CONTROL OF CELL-GROWTH
INTRACELLULAR CA2+ POOL CONTENT IS LINKED TO CONTROL OF CELL-GROWTH
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DOI：
10.1073/pnas.90.11.4986
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
GILL, DL
中科院分区：
文献类型：
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作者：
SHORT, AD;BIAN, JH;GILL, DL
DDT 1 MF-2平滑肌细胞内Ca ~（2+）池的耗竭和再充盈与DNA合成和增殖的发生密切相关。细胞内钙泵抑制剂2，5-二叔丁基对苯二酚（DBHQ）和毒胡萝卜素（TG）特异性地清空相同的肌醇1，4，5-三磷酸（InsP 3）敏感的钙池，并且在对应于钙泵阻断的浓度下都抑制细胞生长。然而，在两种抑制剂之间观察到一个重要的区别，就其作用的可逆性而言。从DBHQ-阻滞的细胞中去除DBHQ后，Ca 2+池立即重新填充，14小时后细胞进入S期，随后正常细胞增殖;进入S期的时间与从汇合阻滞释放的细胞相同。虽然TG不可逆地阻断Ca 2+泵和清空Ca 2+池，TG-逮捕的细胞高血清治疗诱导恢复功能的Ca 2+池在6小时内（通过可能的新泵的合成），此后细胞进行到S期和正常的细胞增殖在相同的时间段内（14小时），以下释放DBHQ-逮捕的细胞。Ca 2+泵阻断和生长停滞之间的精确关系表明，Ca 2+池排空使细胞保持在G 0样静止状态;在重新填充池后，恢复正常的细胞周期进程。这是可能的，一个特定的细胞周期事件所需的G 0到G1的过渡取决于从InsP 3敏感的Ca 2+池产生的信号。
A close correlation was observed between intracellular Ca2+ pool depletion and refilling and the onset of DNA synthesis and proliferation of DDT1MF-2 smooth muscle cells. The intracellular Ca2+ pump inhibitors 2,5-di-tert-butyl-hydroquinone (DBHQ) and thapsigargin (TG) specifically emptied identical inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pools and both arrested cell growth at concentrations corresponding to Ca2+ pump blockade. However, an important distinction was observed between the two inhibitors with respect to their reversibility of action. Upon removal of DBHQ from DBHQ-arrested cells, Ca2+ pools immediately refilled, and 14 hr later cells entered S phase followed by normal cell proliferation; the time for entry into S phase was identical to that for cells released from confluence arrest. Although TG irreversibly blocked Ca2+ pumping and emptied Ca2+ pools, high serum treatment of TG-arrested cells induced recovery of functional Ca2+ pools in 6 hr (via probable synthesis of new pump); thereafter cells proceeded to S phase and normal cell proliferation within the same time period (14 hr) as that following release of DBHQ-arrested cells. The precise relationship between Ca2+ pump blockade and growth arrest indicates that Ca2+ pool emptying maintains cells in a G0-like quiescent state; upon refilling of pools, normal progression into the cell cycle is resumed. It is possible that a specific cell cycle event necessary for G0 to G1 transition depends upon signals generated from the InsP3-sensitive Ca2+ pool.