García-Martínez C, López-Soriano F J, Argilés J M
Departament de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Cancer Lett. 1994 Dec 9;87(2):123-30. doi: 10.1016/0304-3835(94)90212-7.
Rats bearing the Yoshida AH-130 ascites hepatoma, a cachectic rat tumour, showed signs of important muscle wasting with reduced muscle weights. This phenomenon was associated with a decreased rate of in vivo alanine oxidation as measured by the production of 14CO2 from [U-14C]alanine intragastrically administered. It was later found that the decreased amino acid oxidation was associated with a reduced uptake in skeletal muscle as measured in incubated soleus muscles, thus suggesting that the decreased in vivo oxidation is basically due to a reduced oxidation of the amino acid in skeletal muscle. The decrease in alanine oxidation in the tumour-bearing animals was also associated with higher circulating alanine concentrations in their blood. In addition, tumour-bearing rats presented a lower (26%) protein synthetic rate in skeletal muscle, as measured by the incorporation of [14C]phenylalanine into muscle protein. The addition of insulin to the incubation medium abolished the lower rate of protein synthesis, thus suggesting a greater response to this hormone by the muscle of tumour-bearing rats. In conjunction with a reduced protein synthesis, tumour-bearing rats showed a clearly enhanced rate of protein degradation in isolated skeletal muscles. The results presented confirm previous observations suggesting that the skeletal muscle of tumour bearing animals is in a profound negative nitrogen balance which partially accounts for the wasting observed in the tissue. In addition, the present study allows us to conclude that, in spite of the increased alanine utilization for both gluconeogenesis and tumour growth, the oxidation of alanine by the whole animal is decreased in the tumour-bearing rats. This seems to be associated with a decreased ability of skeletal muscle to handle this amino acid.
携带吉田AH - 130腹水肝癌（一种恶病质大鼠肿瘤）的大鼠出现了明显的肌肉萎缩迹象，肌肉重量减轻。这种现象与通过胃内给予[U - 14C]丙氨酸产生14CO2来测量的体内丙氨酸氧化速率降低有关。后来发现，氨基酸氧化减少与在孵育的比目鱼肌中测量到的骨骼肌摄取减少有关，因此表明体内氧化减少基本上是由于骨骼肌中氨基酸氧化减少。荷瘤动物丙氨酸氧化减少也与它们血液中循环丙氨酸浓度升高有关。此外，通过将[14C]苯丙氨酸掺入肌肉蛋白来测量，荷瘤大鼠骨骼肌中的蛋白质合成速率较低（26%）。向孵育培养基中添加胰岛素消除了较低的蛋白质合成速率，因此表明荷瘤大鼠的肌肉对这种激素有更大的反应。与蛋白质合成减少同时，荷瘤大鼠在分离的骨骼肌中蛋白质降解速率明显增强。所呈现的结果证实了先前的观察结果，表明荷瘤动物的骨骼肌处于严重的负氮平衡状态，这部分解释了在该组织中观察到的消瘦现象。此外，本研究使我们能够得出结论，尽管丙氨酸用于糖异生和肿瘤生长的利用率增加，但荷瘤大鼠中整个动物的丙氨酸氧化减少。这似乎与骨骼肌处理这种氨基酸的能力降低有关。
