Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Room 206, 5l Blossom Street, Boston, Massachusetts 02114, USA.
Muscle Nerve. 2013 May;47(5):711-21. doi: 10.1002/mus.23642. Epub 2013 Feb 9.
Immobilization by casting induces disuse muscle atrophy (DMA).
Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis, and inflammation during DMA.
Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius.
Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways.
石膏固定会导致废用性肌肉萎缩(DMA)。
使用野生型(WT)和半胱天冬酶-3 敲除(KO)小鼠,我们评估了半胱天冬酶-3 在 DMA 期间对肌肉质量、细胞凋亡和炎症的影响。
半胱天冬酶-3 缺乏显著减轻了肌肉质量的减少[比目鱼肌:KO 组为 28±1%,WT 组为 41±3%;比目鱼肌:KO 组为 47±2%,WT 组为 56±2%(P<0.05)]和腓肠肌抽搐张力的减少(KO 组为 23±4%,WT 组为 36±3%,P<0.05)在固定侧与对侧后肢的第 14 天。缺乏半胱天冬酶-3 降低了固定诱导的比目鱼肌中凋亡肌核的增加(增加 3.2 倍)和巨噬细胞浸润(增加 2.2 倍),并减弱了腓肠肌中单核细胞趋化蛋白-1mRNA 表达的增加(KO 组为 2 倍,WT 组为 18 倍)。
半胱天冬酶-3 在 DMA 及其相关张力下降中起关键作用,可能通过作用于细胞凋亡和炎症途径。