EFFECTS OF 12-O-TETRADECANOYL-PHORBOL-13-ACETATE ON MYOFIBRIL INTEGRITY AND CA2+ CONTENT IN DEVELOPING MYOTUBES
EFFECTS OF 12-O-TETRADECANOYL-PHORBOL-13-ACETATE ON MYOFIBRIL INTEGRITY AND CA2+ CONTENT IN DEVELOPING MYOTUBES
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DOI：
10.1016/0012-1606(82)90334-7
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发表时间：
1982-01-01
影响因子：
2.7
通讯作者：
HOLTZER, H
中科院分区：
文献类型：
--
作者：
CROOP, J;DUBYAK, G;HOLTZER, H
助致癌剂 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 对形状良好的多核肌管中的[鸡胚]横纹肌原纤维具有迅速和选择性的作用。在 TPA 中 3 天后，肌原纤维装置完全被破坏并很大程度上降解。肌肉特异性轻肌球蛋白和 EM 的荧光标记抗体记录了 TPA 的这种分解代谢作用。完全组装的横纹肌原纤维的这种选择性降解很容易逆转。肌原纤维的重新组装需要从头合成蛋白质。经过 TPA 处理的肌管异常富含自噬体，这是正常肌管中很少观察到的细胞器。 TPA 对肌膜下微丝、线粒体、微管或肌浆网 (SR) 的形态没有明显影响。 TPA 不会改变正常肌管成熟时发生的成纤维细胞型中间 10 nm 丝 (FIF) 的程序性消失。经过 TPA 处理的肌管已耗尽肌原纤维，内部充满了肌肉型中间 10 纳米细丝 (MIF) 的广泛网状结构。该药物对构成膜下微丝的组成性收缩蛋白或假定的成肌细胞或成纤维细胞中的 FIF 没有明显影响，也不影响与这些复制细胞相关的运动。正常肌管成熟时发生的总钙含量显着增加在用 TPA 处理的肌管中不存在。
The cocarcinogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA) has a prompt and selective effect on [chick embryo] striated myofibrils in well-formed, multinucleated myotubes. The myofibrillar apparatus is totally disrupted and largely degraded after 3 days in TPA. Fluorescent-tagged antibodies to muscle-specific light meromyosin and EM document this catabolic effect of TPA. This selective degradation of fully assembled striated myofibrils is readily reversible. This reassembly of myofibrils requires de novo protein synthesis. The TPA-treated myotubes are unusually rich in autophagosomes, organelles rarely observed in normal myotubes. TPA has no discernable effect on the morphology of the subsarcolemmal microfilaments, mitochondria, microtubules or sarcoplasmic reticulum (SR). The programmed disappearance of the fibroblast-type, intermediate 10-nm filaments (FIF) that occurs as normal myotubes mature is not altered by TPA. The TPA-treated myotubes depleted of myofibrils are filled with an extensive meshwork of the muscle-type intermediate 10-nm filaments (MIF). The drug has no obvious effect on the constitutive contractile proteins comprising the submembranous microfilaments, or the FIF in presumptive myoblasts or fibroblasts, nor does it affect the motility associated with these replicating cells. The striking increase in total Ca content which occurs as normal myotubes mature is absent in myotubes treated with TPA.