Activation of caspase 3, 9, 12, and Bax in masseter muscle of mdx mice during necrosis
Activation of caspase 3, 9, 12, and Bax in masseter muscle of mdx mice during necrosis
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DOI：
10.1007/s10974-007-9122-9
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发表时间：
2007-04-01
影响因子：
2.7
通讯作者：
Ide, Y.
中科院分区：
文献类型：
--
作者：
Honda, A.;Abe, S.;Ide, Y.
MDX小鼠是肌肉营养不良症的模型，缺乏肌营养不良蛋白，一种细胞膜蛋白。众所周知，肌营养不良蛋白的缺乏会在出生后2周导致肌肉纤维坏死，到出生4周时，大部分坏死的肌肉纤维会被再生的肌肉纤维所取代。最近的一项研究表明，线粒体介导的细胞内应激可能在肌肉纤维坏死过程中产生，这是一种类似于细胞凋亡的现象，但没有分析内质网介导的细胞内应激。因此，我们检测了参与内质网应激途径的caspase-12基因和参与线粒体应激途径的bax、caspase-9和caspase-3基因在MDX咬肌中的表达。我们发现caspase-12在出生后2-3周的细胞中过度表达，此时肌肉纤维坏死不明显。这表明在没有dystrophin的情况下，应激发生在内质网中以维持细胞的形态。此外，Bax在出生后3周在MDX咬肌中大量表达，caspase-9和-3在出生后3~4周明显表达，坏死和再生明显。这些结果表明，在MDX咬肌坏死过程中产生内质网和线粒体应激，提示这些事件是一种类似于细胞凋亡的现象。
The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that the lack of dystrophin causes muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic muscle fibers are replaced by regenerated muscle fibers by 4 weeks after birth. A recent study indicated the possibility that mitochondria-mediated intracellular stress, a phenomenon similar to apoptosis, may be produced during muscle fiber necrosis, but did not analyze endoplasmic reticulum-mediated intracellular stress. Therefore, we examined the expression of the caspase-12 gene involved in the endoplasmic reticulum stress pathway and the Bax, caspase-9, and caspase-3 genes involved in the mitochondrial stress pathway in the mdx masseter muscle. We found over-expression of caspase-12 in cells at 2-3 weeks after birth when muscle fiber necrosis was not prominent. This suggests that stress occurs in the endoplasmic reticulum to maintain cell morphology in the absence of dystrophin. In addition, Bax was abundantly expressed in the mdx masseter muscle at 3 weeks after birth, and the expression of caspase-9 and -3 was prominent at 3-4 weeks after birth when necrosis and regeneration were marked. These results indicate that endoplasmic reticulum and mitochondrial stresses are produced during necrosis of the mdx masseter muscle, and suggest that these events are a phenomenon similar to apoptosis.