Diffee Gary M, Kalfas Katherine, Al-Majid Sadeeka, McCarthy Donna O
Biodynamics Laboratory, University of Wisconsin, Madison, Wisconsin 53706, USA.
Am J Physiol Cell Physiol. 2002 Nov;283(5):C1376-82. doi: 10.1152/ajpcell.00154.2002.
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.
恶病质在癌症患者中很常见,其特征是严重的肌肉萎缩,但关于癌症恶病质对肌球蛋白等收缩蛋白异构体表达的影响却知之甚少。肌肉萎缩的其他原因会使肌球蛋白异构体的表达向快速(II型)异构体表达增加的方向转变。我们给小鼠注射了鼠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。通过SDS-PAGE测定肌肉匀浆中的肌球蛋白重链(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,所检测的三块肌肉的肌肉质量均显著下降,其中比目鱼肌下降幅度最大。虽然在对照小鼠的比目鱼肌样本中未检测到IIb型MHC,但在荷瘤小鼠的比目鱼肌中,IIb型占总MHC的19%。与对照相比,荷瘤小鼠比目鱼肌中的I型MHC显著降低。在跖肌和腓肠肌中,MHC异构体含量与对照组无显著差异。这些数据首次表明,在癌症恶病质期间,肌肉萎缩伴随着肌球蛋白异构体表达的变化。