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PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice
Cancer cachexia (CC) accounts for 20%–40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201462/ https://www.ncbi.nlm.nih.gov/pubmed/35700525 http://dx.doi.org/10.1139/apnm-2022-0086 |
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author | Morena da Silva, Francielly Rosa-Caldwell, Megan E. Schrems, Eleanor R. Martinez, Lauren Amos, Madeline G. Lim, Seongkyun Cabrera, Ana Regina Brown, Jacob L. Washington, Tyrone A. Greene, Nicholas P. |
author_facet | Morena da Silva, Francielly Rosa-Caldwell, Megan E. Schrems, Eleanor R. Martinez, Lauren Amos, Madeline G. Lim, Seongkyun Cabrera, Ana Regina Brown, Jacob L. Washington, Tyrone A. Greene, Nicholas P. |
author_sort | Morena da Silva, Francielly |
collection | PubMed |
description | Cancer cachexia (CC) accounts for 20%–40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ~11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively (p < 0.05). MitoTimer red:green ratio for male PGC was ~65% higher than WT groups (p < 0.05), with ~3-fold more red puncta in LLC than PBS (p < 0.05). Red:green ratio was 56% lower in females WT-LLC vs PGC-LLC (p < 0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ~73% and 2-fold higher in male and female LLC mice, respectively, vs PBS (p < 0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways. |
format | Online Article Text |
id | pubmed-10201462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-102014622023-05-22 PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice Morena da Silva, Francielly Rosa-Caldwell, Megan E. Schrems, Eleanor R. Martinez, Lauren Amos, Madeline G. Lim, Seongkyun Cabrera, Ana Regina Brown, Jacob L. Washington, Tyrone A. Greene, Nicholas P. Appl Physiol Nutr Metab Article Cancer cachexia (CC) accounts for 20%–40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ~11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively (p < 0.05). MitoTimer red:green ratio for male PGC was ~65% higher than WT groups (p < 0.05), with ~3-fold more red puncta in LLC than PBS (p < 0.05). Red:green ratio was 56% lower in females WT-LLC vs PGC-LLC (p < 0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ~73% and 2-fold higher in male and female LLC mice, respectively, vs PBS (p < 0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways. 2022-09-01 2022-06-14 /pmc/articles/PMC10201462/ /pubmed/35700525 http://dx.doi.org/10.1139/apnm-2022-0086 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Morena da Silva, Francielly Rosa-Caldwell, Megan E. Schrems, Eleanor R. Martinez, Lauren Amos, Madeline G. Lim, Seongkyun Cabrera, Ana Regina Brown, Jacob L. Washington, Tyrone A. Greene, Nicholas P. PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title | PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title_full | PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title_fullStr | PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title_full_unstemmed | PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title_short | PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
title_sort | pgc-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201462/ https://www.ncbi.nlm.nih.gov/pubmed/35700525 http://dx.doi.org/10.1139/apnm-2022-0086 |
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