The molecular basis of skeletal muscle weakness in a mouse model of inflammatory myopathy.
The molecular basis of skeletal muscle weakness in a mouse model of inflammatory myopathy.
复制标题
炎症性肌病小鼠模型骨骼肌无力的分子基础。
DOI：
10.1002/art.34625
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发表时间：
2012-11
影响因子：
--
通讯作者：
Nagaraju, Kanneboyina
中科院分区：
文献类型：
--
作者：
Coley, William;Rayavarapu, Sree;Pandey, Gouri S.;Sabina, Richard L.;Van der Meulen, Jack H.;Ampong, Beryl;Wortmann, Robert L.;Rawat, Rashmi;Nagaraju, Kanneboyina
一般认为，多发性肌炎和皮肌炎患者的肌肉无力是由于自身免疫和炎症过程。然而，已经观察到，在患者中炎症的抑制和肌肉功能的恢复之间存在较差的相关性。因此，我们假设非免疫机制也有助于肌肉无力。特别是，已经提出AMP脱氨酶（AMPD 1）的获得性缺乏可能是肌炎中肌无力的原因。我们在自身免疫性炎症性肌炎的MHC I类小鼠模型中，在炎症发作之前和之后使用了全面的功能、行为、组织学、分子、酶和代谢评估。我们发现，在浸润单核细胞出现之前，小鼠中可检测到肌肉无力和代谢紊乱。肌肉功能的力收缩分析显示，无力与AMDP1表达相关，并且是肌炎特异性的。我们还证明，AMPD 1表达降低会导致健康小鼠肌肉力量下降。纤维分型表明，随着肌炎的进展，快缩肌转化为慢缩肌，微阵列结果表明，AMPD 1和其他嘌呤核苷酸途径基因受到抑制，沿着糖酵解所必需的基因。这些数据表明，AMPD 1缺乏症是在明显的肌肉炎症之前获得的，并且至少部分地是肌炎小鼠模型中发生的肌肉无力的原因。因此，AMPD 1是肌炎的潜在治疗靶点。
It is generally believed that muscle weakness in patients with polymyositis and dermatomyositis is due to autoimmune and inflammatory processes. However, it has been observed that there is a poor correlation between the suppression of inflammation and a recovery of muscle function in patients. We have therefore hypothesized that non-immune mechanisms also contribute to muscle weakness. In particular, it has been suggested that an acquired deficiency of AMP deaminase (AMPD1) may be responsible for muscle weakness in myositis. We have used comprehensive functional, behavioral, histological, molecular, enzymatic and metabolic assessments before and after the onset of inflammation in MHC class I mouse model of autoimmune inflammatory myositis. We found that muscle weakness and metabolic disturbances were detectable in the mice prior to the appearance of infiltrating mononuclear cells. Force contraction analysis of muscle function revealed that weakness was correlated with AMDP1 expression and was myositis-specific. We also demonstrated that decreasing AMPD1 expression results in decreased muscle strength in healthy mice. Fiber typing suggested that fast-twitch muscles are converted to slow-twitch muscles as myositis progresses, and microarray results indicated that AMPD1 and other purine nucleotide pathway genes are suppressed, along with genes essential to glycolysis. These data suggest that an AMPD1 deficiency is acquired prior to overt muscle inflammation and is responsible, at least in part, for the muscle weakness that occurs in the mouse model of myositis. AMPD1 is therefore a potential therapeutic target in myositis.
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影响因子：
3
作者：
Norman, Barbara;Nygren, Anders T.;Sabina, Richard L.
通讯作者：
Sabina, Richard L.
影响因子：
3.4
作者：
Parker, Kenneth C.;Kong, Sek Won;Walsh, Ronan J.;Salajegheh, Mohammad;Moghadaszadeh, Behzad;Amato, Anthony A.;Nazareno, Remedios;Lin, Yin Yin;Krastins, Bryan;Sarracino, David A.;Beggs, Alan H.;Pinkus, Jack L.;Greenberg, Steven A.
通讯作者：
Greenberg, Steven A.
影响因子：
4.8
作者：
Sims, B;Mahnke-Zizelman, KM;Theibert, AB
通讯作者：
Theibert, AB
DOI：
10.1073/pnas.97.16.9209
发表时间：
2000-08-01
影响因子：
11.1
作者：
Nagaraju, K;Raben, N;Plotz, P
通讯作者：
Plotz, P
影响因子：
11.2
作者：
Lunemann, Jan D.;Schmidt, Jens;Munz, Christian
通讯作者：
Munz, Christian