Endoplasmic reticulum stress-induced apoptosis in pre-necrotic period in skeletal muscles of laminin-2 deficiency

围产期大量坏死后再生过程流产导致缺乏层粘连蛋白-2的骨骼肌营养不良。虽然这种凋亡肌纤维损失似乎是锚定依赖性的或不正常的，但导致细胞凋亡的缺陷信号通路尚未被确定。在这项研究中，我们检测了层粘连蛋白a2链零突变小鼠dy3K/dy3K再生纤维中受到干扰的信号通路。dy3K/dy3K再生纤维显示Bad的Ser 112和135磷酸化，但Ser 155磷酸化。Bad的Ser 155通过PKA的激活而磷酸化。因此，通过PKA的存活信号通路可能在dy3K/dy3K再生纤维中受到干扰。此外，我们检测了dy3K/dy3K坏死前时期的骨骼肌。dy3K/dy3K组在出生后第10天突然出现大量坏死。我们发现caspase-12在出生后第9天激活。因此，内质网（ER）应激诱导的凋亡似乎发生在dy3K/dy3K肌纤维坏死之前。

Abortive regeneration process following massive necrosis in perinatal period causes dystrophic changes in laminin-2 deficient skeletal muscles. Although this apoptotic muscle fiber loss seems to be anchorage-dependent or anoikis, defective signaling pathways resulting in apoptosis have not been identified, yet.In this study, we examined the signaling pathways disturbed in regenerating fibers of dy3K/dy3K, a null mutant mouse for laminin a2 chain. Regenerating fibers of dy3K/dy3K showed phosphorylation of Ser 112 and 135 of Bad, but of Ser 155. Ser 155 of Bad is phosphorylated via activation of PKA. Therefore, it is possible that the survival signaling pathway via PKA is disturbed in regenerating fibers of dy3K/dy3K.In addition, we examined skeletal muscles in the pre-necrosis period of dy3K/dy3K. In dy3K/dy3K, massive necrosis occurs suddenly on postnatal day 10. We found the activation of caspase-12 on postnatal day 9. Accordingly, the endoplasmic reticulum (ER) stress-induced apoptosis seems to take place just before the necrosis of muscle fibers in dy3K/dy3K.