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

内质网应激诱导层粘连蛋白2缺陷骨骼肌坏死前期细胞凋亡

• 批准号: 14570605
• 负责人: IKEZOE Koji
• 金额: $ 2.56万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570605/
• 关键词: apoptosis; laminin-2; merosin; anoikis; Bad; caspase-12; ER stress; 小胞体ストレス性アポトーシス; 筋小胞体; ジスフェルリン; 筋ジストロフィー

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.

围产期大量坏死后流产的再生过程会导致层粘连蛋白-2缺乏的骨骼肌发生营养不良变化。虽然这种凋亡的肌纤维丢失似乎是锚定依赖或失巢凋亡，但导致细胞凋亡的信号通路缺陷尚未被识别。在这项研究中，我们研究了层粘连蛋白a2链的缺失突变小鼠dy3K/dy3K再生纤维中受到干扰的信号通路。Dy3K/dy3K的再生纤维表现为Bad的Ser112和135的磷酸化，而Ser155的磷酸化。Bad的Ser 155通过激活PKA而被磷酸化。因此，可能在dy3K/dy3K的再生纤维中，通过PKA的生存信号通路受到干扰。此外，我们还观察了dy3K/dy3K的前坏死期的骨骼肌。在dy3K/dy3K中，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天被激活。相应地，内质网(ER)应激诱导的细胞凋亡似乎发生在dy3K/dy3K中肌纤维坏死之前。

项目成果

HTLV-1-associated myelopathy/tropical spastic pararesis accompanied with psoriasis.

HTLV-1相关脊髓病/热带痉挛性截瘫伴有牛皮癣。

• 发表时间: 2004
• 期刊: J Neurol Sci 221(1-2)
• 作者: Watanabe A;et al.
• 通讯作者: et al.

Ikezoe K et al.: "Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy"Acta Neuropathol(Ber1). (in press). (2004)

Ikezoe K 等人：“致死性还原体肌病肌核中 DNA 碎片的超微结构检测”Acta Neuropathol (Ber1)。

Dysferlin expression in tubular aggregates : their possible relationship to endoplasmic stress

管状聚集体中的 Dysferlin 表达：与内质应激的可能关系

• 发表时间: 2003
• 期刊: Acta Neuropathol (Berl) 105
• 作者: Ikezoe k et al.

Watanabe A et al.: "HTLV-1-associated myelopathy/tropical spastic paraparesis accompanied with psoriasis"J Neurol Sci. (in press). (2004)

Watanabe A 等人：“HTLV-1 相关脊髓病/伴有银屑病的热带痉挛性截瘫”J Neurol Sci。

HTLV-1-associated myelopathy/tropical spastic paraparesis accompanied with psoriasis

HTLV-1相关性脊髓病/热带痉挛性截瘫伴有银屑病

• 发表时间: 2004
• 期刊: J Neurol Sci 221
• 作者: Watanabe A et al.