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Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium.

Wang H, Li TL, Hsia S, Su IL, Chan YL, Wu CJ - Oncotarget (2015)

Bottom Line: In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation.In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy.The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.

ABSTRACT
Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

No MeSH data available.


Related in: MedlinePlus

mRNA and protein levels for genes encoding cachexic factors towards proteolytic signaling molecules after line-1 tumor inoculation (protocol #1)(A) Western blot analysis for expressions of IL-6, TNF-α, myostatin and β-actin in gastrocnemius muscles from line-1 tumor-bearing mice. The graph represents relative densitometric intensity of each band normalized to β-actin. (B) mRNA levels (left) and protein levels (right) for genes of cachexic factors and proteolysis relative signaling molecules in gastrocnemius muscle. Values are means of fluorescence signals expressed as a percentage of healthy control mice, and normalization to the GAPDH mRNA amount. (C) Immunohistochemistry of gastrocnemius muscle from tumor-bearing mice, where protein expressions are shown for MAFbx (top), MuRF-1(middle) and NF-κB (bottom). Data are shown as mean ± SD. n = 5–8 mice/group and each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
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Figure 3: mRNA and protein levels for genes encoding cachexic factors towards proteolytic signaling molecules after line-1 tumor inoculation (protocol #1)(A) Western blot analysis for expressions of IL-6, TNF-α, myostatin and β-actin in gastrocnemius muscles from line-1 tumor-bearing mice. The graph represents relative densitometric intensity of each band normalized to β-actin. (B) mRNA levels (left) and protein levels (right) for genes of cachexic factors and proteolysis relative signaling molecules in gastrocnemius muscle. Values are means of fluorescence signals expressed as a percentage of healthy control mice, and normalization to the GAPDH mRNA amount. (C) Immunohistochemistry of gastrocnemius muscle from tumor-bearing mice, where protein expressions are shown for MAFbx (top), MuRF-1(middle) and NF-κB (bottom). Data are shown as mean ± SD. n = 5–8 mice/group and each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.

Mentions: The factors that cause muscle atrophy were examined, we analyzed cytokines and atrophy-related genes in tumor-bearing mice. First, western blotting analysis revealed that: TNF-α was up-regulated in moderate cachexia mice (Figure 3A and B); the serum level of IL-6 was significantly elevated, while its expression in the gastrocnemius muscle remained within the normal range; the serum level of myostatin in the gastrocnemius muscle also increased. Added together, TNF-α and myostatin are likely the key mediators that promote proteolysis.


Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium.

Wang H, Li TL, Hsia S, Su IL, Chan YL, Wu CJ - Oncotarget (2015)

mRNA and protein levels for genes encoding cachexic factors towards proteolytic signaling molecules after line-1 tumor inoculation (protocol #1)(A) Western blot analysis for expressions of IL-6, TNF-α, myostatin and β-actin in gastrocnemius muscles from line-1 tumor-bearing mice. The graph represents relative densitometric intensity of each band normalized to β-actin. (B) mRNA levels (left) and protein levels (right) for genes of cachexic factors and proteolysis relative signaling molecules in gastrocnemius muscle. Values are means of fluorescence signals expressed as a percentage of healthy control mice, and normalization to the GAPDH mRNA amount. (C) Immunohistochemistry of gastrocnemius muscle from tumor-bearing mice, where protein expressions are shown for MAFbx (top), MuRF-1(middle) and NF-κB (bottom). Data are shown as mean ± SD. n = 5–8 mice/group and each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480714&req=5

Figure 3: mRNA and protein levels for genes encoding cachexic factors towards proteolytic signaling molecules after line-1 tumor inoculation (protocol #1)(A) Western blot analysis for expressions of IL-6, TNF-α, myostatin and β-actin in gastrocnemius muscles from line-1 tumor-bearing mice. The graph represents relative densitometric intensity of each band normalized to β-actin. (B) mRNA levels (left) and protein levels (right) for genes of cachexic factors and proteolysis relative signaling molecules in gastrocnemius muscle. Values are means of fluorescence signals expressed as a percentage of healthy control mice, and normalization to the GAPDH mRNA amount. (C) Immunohistochemistry of gastrocnemius muscle from tumor-bearing mice, where protein expressions are shown for MAFbx (top), MuRF-1(middle) and NF-κB (bottom). Data are shown as mean ± SD. n = 5–8 mice/group and each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
Mentions: The factors that cause muscle atrophy were examined, we analyzed cytokines and atrophy-related genes in tumor-bearing mice. First, western blotting analysis revealed that: TNF-α was up-regulated in moderate cachexia mice (Figure 3A and B); the serum level of IL-6 was significantly elevated, while its expression in the gastrocnemius muscle remained within the normal range; the serum level of myostatin in the gastrocnemius muscle also increased. Added together, TNF-α and myostatin are likely the key mediators that promote proteolysis.

Bottom Line: In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation.In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy.The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.

ABSTRACT
Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

No MeSH data available.


Related in: MedlinePlus