Influenza Infection has Fiber Type-Specific Effects on Cellular and Molecular Skeletal Muscle Function in Aged Mice.
Influenza Infection has Fiber Type-Specific Effects on Cellular and Molecular Skeletal Muscle Function in Aged Mice.
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流感感染对老年小鼠的细胞和分子骨骼肌功能具有纤维类型特异性影响。
DOI：
10.1093/gerona/glaa136
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Miller,MarkS
中科院分区：
文献类型：
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作者：
Straight,ChadR;Ringham,OliviaR;Bartley,JennaM;Keilich,SpencerR;Kuchel,GeorgeA;Haynes,Laura;Miller,MarkS
骨骼肌肌病是流感感染的常见非肺部表现，导致老年人身体功能下降和住院治疗。然而，对潜在的机制仍然知之甚少。我们的研究检查了流感病毒A肺部感染对老年（20个月）C57 BL/6雄性小鼠比目鱼肌和趾长伸肌细胞（单纤维）和分子（肌球蛋白-肌动蛋白相互作用和肌丝特性）水平收缩功能的影响，这些小鼠是健康的或流感感染7天（感染后7天; 7-DPI）或12天（12-DPI）。肌球蛋白重链（MHC）IIA和IIB纤维的横截面积（CSA）在12 DPI时相对于7 DPI和健康人减少。相对于7-DPI和健康人，MHC IIA纤维中的最大等长力在12-DPI时也降低，导致比力（最大等长力除以CSA）没有变化。相比之下，MHC IIB纤维产生更大的等长力和比力在7-DPI相比，12-DPI或健康。MHC IIB纤维中的比力增加可能是由于更大的肌丝晶格刚度和/或强烈结合的肌球蛋白-肌动蛋白交叉桥的数量或刚度增加。在分子水平上，跨桥动力学在感染的MHC IIA纤维中较慢，而在MHC IIB纤维中的变化基本上是不存在的。在这两种纤维类型中，更大的肌丝晶格刚度与比力呈正相关。这项研究提供了新的证据，表明细胞和分子收缩功能受到流感感染的影响，在纤维类型特异性的方式，建议潜在的分子机制，以帮助解释流感引起的肌病的影响。
Skeletal muscle myopathies represent a common non-pulmonary manifestation of influenza infection, leading to reduced physical function and hospitalization in older adults. However, underlying mechanisms remain poorly understood. Our study examined the effects of influenza virus A pulmonary infection on contractile function at the cellular (single fiber) and molecular (myosin-actin interactions and myofilament properties) levels in soleus and extensor digitorum longus muscles of aged (20 months) C57BL/6 male mice that were healthy or flu-infected for 7 (7-days post-infection; 7-DPI) or 12 days (12-DPI). Cross-sectional area (CSA) of myosin heavy chain (MHC) IIA and IIB fibers was reduced at 12-DPI relative to 7-DPI and healthy. Maximal isometric force in MHC IIA fibers was also reduced at 12-DPI relative to 7-DPI and healthy, resulting in no change in specific force (maximal isometric force divided by CSA). In contrast, MHC IIB fibers produced greater isometric force and specific force at 7-DPI compared to 12-DPI or healthy. The increased specific force in MHC IIB fibers was likely due to greater myofilament lattice stiffness and/or an increased number or stiffness of strongly bound myosin-actin cross-bridges. At the molecular level, cross-bridge kinetics were slower in MHC IIA fibers with infection, while changes in MHC IIB fibers were largely absent. In both fiber types, greater myofilament lattice stiffness was positively related to specific force. This study provides novel evidence that cellular and molecular contractile function is impacted by influenza infection in a fiber type-specific manner, suggesting potential molecular mechanisms to help explain the impact of flu-induced myopathies.