Altered expression of skeletal muscle myosin isoforms in cancer cachexia

Altered expression of skeletal muscle myosin isoforms in cancer cachexia
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DOI:
10.1152/ajpcell.00154.2002
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发表时间:
2002-11-01
影响因子:
5.5
通讯作者:
McCarthy, DO
McCarthy, DO
中科院分区:
生物学2区
文献类型:
--
作者:
Diffee, GM;Kalfas, K;McCarthy, DO

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恶病质在癌症中常见,其特征是严重的肌肉萎缩,但关于癌症恶病质对收缩蛋白亚型如肌球蛋白表达的影响知之甚少。肌萎缩的其他原因使肌球蛋白亚型的表达向快速(II型)亚型表达增加转变。我们给小鼠注射了小鼠C-26腺癌细胞,这是一种已被证明会导致肌肉萎缩的肿瘤细胞系。在肿瘤注射后21天处死小鼠,并取出后肢肌肉。用SDS-PAGE法测定肌肉匀浆中肌球蛋白重链(MHC)和肌球蛋白轻链(MLC)含量。荷瘤(T)小鼠的体重显著降低。与对照组相比,测试的所有三块肌肉的肌肉质量均显著减少,其中比目鱼肌的减少幅度最大。虽然没有检测到IIb型MHC在比目鱼肌样品从对照小鼠,IIb型占19%的总MHC在比目鱼肌。与对照比目鱼肌相比,T中I型MHC显著降低。在跖肌和腓肠肌中,MHC亚型含量与对照组无显著差异。这些数据是第一个显示在癌性恶病质期间伴随肌肉萎缩的肌球蛋白亚型表达的变化。
Cachexia is commonly seen in cancer and is characterized by severe muscle wasting, but little is known about the effect of cancer cachexia on expression of contractile protein isoforms such as myosin. Other causes of muscle atrophy shift expression of myosin isoforms toward increased fast (type II) isoform expression. We injected mice with murine C-26 adenocarcinoma cells, a tumor cell line that has been shown to cause muscle wasting. Mice were killed 21 days after tumor injection, and hindlimb muscles were removed. Myosin heavy chain (MHC) and myosin light chain (MLC) content was determined in muscle homogenates by SDS-PAGE. Body weight was significantly lower in tumor-bearing (T) mice. There was a significant decrease in muscle mass in all three muscles tested compared with control, with the largest decrease occurring in the soleus. Although no type IIb MHC was detected in the soleus samples from control mice, type IIb comprised 19% of the total MHC in T soleus. Type I MHC was significantly decreased in T vs. control soleus muscle. MHC isoform content was not significantly different from control in plantaris and gastrocnemius muscles. These data are the first to show a change in myosin isoform expression accompanying muscle atrophy during cancer cachexia.