دورية أكاديمية
Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice
| العنوان: | Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice |
|---|---|
| المؤلفون: | Brown, Jacob L., Lee, David E., Rosa-Caldwell, Megan E., Brown, Lemuel A., Perry, Richard A., Haynie, Wesley S., Huseman, Kendra, Sataranatarajan, Kavithalakshmi, Van Remmen, Holly, Washington, Tyrone A., Wiggs, Michael P., Greene, Nicholas P. |
| المصدر: | Health and Kinesiology Faculty Publications and Presentations |
| بيانات النشر: | Scholar Works at UT Tyler |
| سنة النشر: | 2018 |
| المجموعة: | Scholar Works at UT Tyler (University of Texas at Tyler) |
| مصطلحات موضوعية: | Protein synthesis, LLC, Ubiquitin, MAPK, ERK, p38, Kinesiology |
| الوصف: | Background: Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer-related death. The mechanisms controlling development of tumour-induced muscle wasting are not fully elucidated. Specifically, the progression and development of cancer cachexia are underexplored. Therefore, we examined skeletal muscle protein turnover throughout the development of cancer cachexia in tumour-bearing mice. Methods: Lewis lung carcinoma (LLC) was injected into the hind flank of C57BL6/J mice at 8 weeks age with tumour allowed to develop for 1, 2, 3, or 4 weeks and compared with PBS injected control. Muscle size was measured by cross-sectional area analysis of haematoxylin and eosin stained tibialis anterior muscle. 2H2O was used to assess protein synthesis throughout the development of cancer cachexia. Immunoblot and RT-qPCR were used to measure regulators of protein turnover. TUNEL staining was utilized to measure apoptotic nuclei. LLC conditioned media (LCM) treatment of C2C12 myotubes was used to analyse cancer cachexia in vitro. Results: Muscle cross-sectional area decreased ~40% 4 weeks following tumour implantation. Myogenic signalling was suppressed in tumour-bearing mice as soon as 1 week following tumour implantation, including lower mRNA contents of Pax7, MyoD, CyclinD1, and Myogenin, when compared with control animals. AchRδ and AchRε mRNA contents were down-regulated by ~50% 3 weeks following tumour implantation. Mixed fractional synthesis rate protein synthesis was ~40% lower in 4 week tumour-bearing mice when compared with PBS controls. Protein ubiquitination was elevated by ~50% 4 weeks after tumour implantation. Moreover, there was an increase in autophagy machinery after 4 weeks of tumour growth. Finally, ERK and p38 MAPK phosphorylations were fourfold and threefold greater than control muscle 4 weeks following tumour implantation, respectively. Inhibition of p38 MAPK, but not ERK MAPK, in vitro partially rescued LCM-induced loss of myotube diameter. Conclusions: Our ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://scholarworks.uttyler.edu/hkdept_fac/33Test; https://scholarworks.uttyler.edu/context/hkdept_fac/article/1035/viewcontent/Protein_20imbalance_20in_20the_20development_20of_20skeletal_20muscle_20wasting_20in.pdfTest |
| الإتاحة: | https://scholarworks.uttyler.edu/hkdept_fac/33Test https://scholarworks.uttyler.edu/context/hkdept_fac/article/1035/viewcontent/Protein_20imbalance_20in_20the_20development_20of_20skeletal_20muscle_20wasting_20in.pdfTest |
| رقم الانضمام: | edsbas.64E90146 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |