Space shuttle flight (STS-90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin-proteasome pathway
Space shuttle flight (STS-90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin-proteasome pathway
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DOI：
10.1096/fj.00-0629fje
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发表时间：
2001-05-01
期刊：
影响因子：
4.8
通讯作者：
Kishi, K
中科院分区：
文献类型：
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作者：
Ikemoto, M;Nikawa, T;Kishi, K
为了阐明微重力诱导的肌肉萎缩的机制，我们重点研究了暴露于16 d航天（STS-90）的新生大鼠萎缩腓肠肌中快型肌球蛋白重链（MHC）降解和蛋白酶表达。太空飞行刺激了蛋白质的泛素化，包括MHC分子，以及肌肉中MHC降解片段的积累。半定量逆转录聚合酶链反应显示，与地面对照大鼠相比，太空飞行显著增加了肌肉中组织蛋白酶L，蛋白酶体组分（RC 2和RC 9），聚泛素和泛素结合酶的mRNA水平。μ-钙蛋白酶、m-钙蛋白酶、组织蛋白酶B和组织蛋白酶H mRNA的水平没有因航天飞行而改变。我们还发现，大鼠尾部悬吊10 d或更长时间导致腓肠肌中MHC的泛素化和降解，正如在航天大鼠中观察到的那样。在悬吊大鼠的肌肉中，这些变化与蛋白酶体的激活以及蛋白酶体组分和聚泛素的mRNA表达上调密切相关。给予半胱氨酸蛋白酶抑制剂E-64并不能阻止悬浮大鼠的MHC降解。我们的研究结果表明，太空飞行可能通过泛素依赖性蛋白水解途径诱导肌肉收缩蛋白（包括MHC）的降解。
To elucidate the mechanisms of microgravity‐induced muscle atrophy, we focused on fast‐type myosin heavy chain (MHC) degradation and expression of proteases in atrophied gastrocnemius muscles of neonatal rats exposed to 16‐d spaceflight (STS‐90). The spaceflight stimulated ubiquitination of proteins, including a MHC molecule, and accumulation of MHC degradation fragments in the muscles. Semiquantitative reverse transcriptase‐polymerase chain reaction revealed that the spaceflight significantly increased mRNA levels of cathepsin L, proteasome components (RC2 and RC9), polyubiquitin, and ubiquitin‐conjugating enzyme in the muscles, compared with those of ground control rats. The levels of μ‐calpain, m‐calpain, cathepsin B, and cathepsin H mRNAs were not changed by the spaceflight. We also found that tail‐suspension of rats for 10 d or longer caused the ubiquitination and degradation of MHC in gastrocnemius muscle, as was observed in the spaceflight rats. In the muscle of suspended rats, these changes were closely associated with activation of proteasome and up‐regulation of expression of mRNA for the proteasome components and polyubiquitin. Administration of a cysteine protease inhibitor, E‐64, to the suspended rats did not prevent the MHC degradation. Our results suggest that spaceflight induces the degradation of muscle contractile proteins, including MHC, possibly through a ubiquitin‐dependent proteolytic pathway.