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

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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.