| Autor: |
Lim, Seongkyun, William Deaver, J., Rosa-Caldwell, Megan E., Haynie, Wesley S., da Silva, Francielly Morena, Cabrera, Ana Regina, Schrems, Eleanor R., Saling, Landen W., Jansen, Lisa T., Dunlap, Kirsten R., Wiggs, Michael P., Washington, Tyrone A., Greene, Nicholas P. |
| Předmět: |
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| Zdroj: |
Journal of Applied Physiology; Jan2022, Vol. 132 Issue 1, p58-72, 15p |
| Abstrakt: |
Cancer cachexia (CC) results in impaired muscle function and quality of life and is the primary cause of death for ~20%–30% of patients with cancer. We demonstrated mitochondrial degeneration as a precursor to CC in male mice; however, whether such alterations occur in females is currently unknown. The purpose of this study was to elucidate muscle alterations in CC development in female tumor-bearing mice. Sixty female C57BL/6J mice were injected with PBS or Lewis lung carcinoma at 8 wk of age, and tumors developed for 1, 2, 3, or 4 wk to assess the time course of cachectic development. In vivo muscle contractile function, protein fractional synthetic rate (FSR), protein turnover, and mitochondrial health were assessed. Three- and four-week tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. HT mice exhibited lower soleus, tibialis anterior, and fat weights than PBS mice. HT mice showed lower peak isometric torque and slower one-half relaxation time than PBS mice. HT mice had lower FSR than PBS mice, whereas E3 ubiquitin ligases were greater in HT than in other groups. Bnip3 (mitophagy) and pMitoTimer red puncta (mitochondrial degeneration) were greater in HT mice, whereas Pgc1α1 and Tfam (mitochondrial biogenesis) were lower in HT mice than in PBS mice. We demonstrate alterations in female tumor-bearing mice where HT exhibited greater protein degradation, impaired muscle contractility, and mitochondrial degeneration compared with other groups. Our data provide novel evidence for a distinct cachectic development in tumorbearing female mice compared with previous male studies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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