Figueras Maite, Busquets Sílvia, Carbó Neus, Almendro Vanessa, Argilés Josep M, López-Soriano Francisco J
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
Int J Oncol. 2005 Sep;27(3):855-60.
The mRNA content of both TNF-alpha and its receptors (TNFR1 and TNFR2) in skeletal muscle and adipose tissue from cachectic rats has been assessed. The implantation of the Yoshida AH-130 ascites hepatoma resulted in substantial decrease in skeletal muscle TNF-alpha expression as early as at day 2 following tumour implantation. However, the mRNA content for the two receptors followed a different pattern, being significantly increased at day 7. In adipose tissue the expression of the TNF-alpha gene was significantly increased at all the time points studied, whereas TNF-alpha receptors expression followed a similar pattern to that observed in skeletal muscle. Western blot analysis indicated that the TNFR1 protein followed an identical pattern to that observed in the mRNA content both in muscle and adipose tissue. It is concluded that, during experimental cancer cachexia, the contribution of muscle-produced TNF-alpha is decreased; however, significant changes were observed in relation with TNF-alpha receptors at the skeletal muscle level that could possibly be related to the muscle wasting process associated with tumour growth.
已对恶病质大鼠骨骼肌和脂肪组织中肿瘤坏死因子-α(TNF-α)及其受体(TNFR1和TNFR2)的mRNA含量进行了评估。吉田AH-130腹水肝癌的植入早在肿瘤植入后第2天就导致骨骼肌TNF-α表达大幅下降。然而,两种受体的mRNA含量呈现不同模式,在第7天显著增加。在脂肪组织中,TNF-α基因的表达在所有研究时间点均显著增加,而TNF-α受体的表达与在骨骼肌中观察到的模式相似。蛋白质印迹分析表明,TNFR1蛋白在肌肉和脂肪组织中的模式与在mRNA含量中观察到的相同。得出的结论是,在实验性癌症恶病质期间,肌肉产生的TNF-α的作用降低;然而,在骨骼肌水平上观察到与TNF-α受体相关的显著变化,这可能与肿瘤生长相关的肌肉消瘦过程有关。