Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy.
Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy.
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DOI：
10.1371/journal.pone.0168846
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sobue G
中科院分区：
文献类型：
--
作者：
Yamada S;Hashizume A;Hijikata Y;Inagaki T;Suzuki K;Kondo N;Kawai K;Noda S;Nakanishi H;Banno H;Hirakawa A;Koike H;Halievski K;Jordan CL;Katsuno M;Sobue G
本研究的目的是表征脊髓和延髓肌萎缩症（SBMA）受试者的呼吸功能特征，并通过比较该疾病与肌萎缩侧索硬化症（ALS）的临床和生化指标来探讨潜在的病理机制。我们招募了患有 SBMA (n = 40) 和 ALS (n = 25) 的男性受试者以及 15 名健康对照受试者，并评估了他们的呼吸功能、运动功能和肌肉力量。与对照组相比，SBMA 受试者的呼气峰流量 (%PEF) 和用力肺活量的预测值有所下降。在 SBMA 中，这两个值都与运动功能测试的躯干分项评分密切相关，并且显示出相对于疾病持续时间的恶化。与日常生活活动（ADL）匹配的 ALS 受试者相比，SBMA 受试者的 %PEF、舌压和握力显着下降。免疫荧光和 RT-PCR 均表明，在 SBMA 受试者中，编码特定于快肌纤维的肌球蛋白重链的基因的表达水平选择性降低。与 ALS 和对照组相比，SBMA 中过氧化物酶体增殖物激活受体 γ 共激活剂 1-α 和过氧化物酶体增殖物激活受体 δ 的 mRNA 水平上调。总之，%PEF 是 SBMA 严重程度和进展的疾病特异性呼吸标志物。 SBMA 受试者的爆发性肌肉力量（包括 %PEF）选择性受到影响，并且与骨骼肌中线粒体生物发生相关分子途径的激活有关。
The aim of this study was to characterize the respiratory function profile of subjects with spinal and bulbar muscular atrophy (SBMA), and to explore the underlying pathological mechanism by comparing the clinical and biochemical indices of this disease with those of amyotrophic lateral sclerosis (ALS). We enrolled male subjects with SBMA (n = 40) and ALS (n = 25) along with 15 healthy control subjects, and assessed their respiratory function, motor function, and muscle strength. Predicted values of peak expiratory flow (%PEF) and forced vital capacity were decreased in subjects with SBMA compared with controls. In SBMA, both values were strongly correlated with the trunk subscores of the motor function tests and showed deterioration relative to disease duration. Compared with activities of daily living (ADL)-matched ALS subjects, %PEF, tongue pressure, and grip power were substantially decreased in subjects with SBMA. Both immunofluorescence and RT-PCR demonstrated a selective decrease in the expression levels of the genes encoding the myosin heavy chains specific to fast-twitch fibers in SBMA subjects. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and peroxisome proliferator-activated receptor delta were up-regulated in SBMA compared with ALS and controls. In conclusion, %PEF is a disease-specific respiratory marker for the severity and progression of SBMA. Explosive muscle strength, including %PEF, was selectively affected in subjects with SBMA and was associated with activation of the mitochondrial biogenesis-related molecular pathway in skeletal muscles.
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影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
14.5
作者：
Atsuta, Naoki;Watanabe, Hirohisa;Sobue, Gen
通讯作者：
Sobue, Gen
影响因子：
9.9
作者：
Fratta, Pietro;Nirmalananthan, Niranjanan;Hanna, Michael G.
通讯作者：
Hanna, Michael G.
影响因子：
3.1
作者：
Mayer, O. H.;Finkel, R. S.;Meier, T.
通讯作者：
Meier, T.
影响因子：
64.8
作者：
LASPADA, AR;WILSON, EM;FISCHBECK, KH
通讯作者：
FISCHBECK, KH