Department of Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
Br J Cancer. 2014 Aug 26;111(5):903-8. doi: 10.1038/bjc.2014.379. Epub 2014 Aug 7.
Cachexia in both mice and humans is associated with tumour production of a sulphated glycoprotein called proteolysis-inducing factor (PIF). In mice PIF binds with high affinity to a surface receptor in skeletal muscle, but little is known about the human receptor. This study compares the human PIF receptor with the murine.
Human PIF was isolated from the G361 melanoma and murine PIF from the MAC16 colon adenocarcinoma. The human PIF receptor was isolated from human skeletal muscle myotubes. Protein synthesis and degradation induced by human and murine PIF was studied in human and murine skeletal muscle myotubes.
Both the human and murine PIF receptors showed the same immunoreactivity and Mr 40 000. Both murine and human PIF inhibited total protein synthesis and stimulated protein degradation in human and murine myotubes to about the same extent, and this was attenuated by a rabbit polyclonal antibody to the murine PIF receptor, but not by a non-specific rabbit antibody. Both murine and human PIF increased the activity of the ubiquitin-proteasome pathway in both human and murine myotubes, as evidenced by an increased 'chymotrypsin-like' enzyme activity, protein expression of the 20S and 19S proteasome subunits, and increased expression of the ubiquitin ligases MuRF1 and MAFbx, and this was also attenuated by the anti-mouse PIF receptor antibody.
These results suggest that the murine and human PIF receptors are identical.
无论是在老鼠还是人类中，恶病质都与肿瘤产生一种称为蛋白水解诱导因子（PIF）的硫酸化糖蛋白有关。在老鼠中，PIF 与骨骼肌中的表面受体具有高亲和力结合，但对人类受体知之甚少。本研究比较了人类和鼠的 PIF 受体。
从 G361 黑色素瘤中分离出人 PIF，从 MAC16 结肠腺癌中分离出鼠 PIF。从人骨骼肌肌管中分离出人 PIF 受体。研究了人源和鼠源 PIF 对人源和鼠源骨骼肌肌管中蛋白合成和降解的影响。
人和鼠的 PIF 受体均显示出相同的免疫反应性和 40000 Mr。人和鼠的 PIF 均抑制人源和鼠源肌管中的总蛋白合成并刺激蛋白降解，这种作用被针对鼠 PIF 受体的兔多克隆抗体减弱，但非特异性兔抗体则没有减弱。人和鼠的 PIF 均增加了人源和鼠源肌管中泛素-蛋白酶体途径的活性，这表现为“糜蛋白酶样”酶活性增加、20S 和 19S 蛋白酶体亚基的蛋白表达增加以及泛素连接酶 MuRF1 和 MAFbx 的表达增加，这种作用也被抗鼠 PIF 受体抗体减弱。
这些结果表明，鼠和人 PIF 受体是相同的。
