α-linolenic acid reduces TNF-induced apoptosis in C2C12 myoblasts by regulating expression of apoptotic proteins

Carotenuto, Felicia; Coletti, Dario; Nardo, Paolo Di; Teodori, Laura

doi:10.4081/ejtm.2016.6033

Cited by 34 publications

(18 citation statements)

References 27 publications

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“…Moreover, a recent study shows that Dox induces apoptosis in rat soleus muscle [ 20 , 21 ]. Data from another recent study shows that TNF- α -induced apoptosis in C2C12 myoblast cells involves a decrease in the BCL2 to BAX ratio, which is consistent with our data [ 37 ]. The current study corroborates the previously published muscle studies on Dox-induced muscle apoptosis.…”

Section: Discussionsupporting

confidence: 93%

Secreted Frizzled‐Related Protein‐2 Inhibits Doxorubicin‐Induced Apoptosis Mediated through the Akt‐mTOR Pathway in Soleus Muscle

Merino

Singla

2018

Oxidative Medicine and Cellular Longevity

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Doxorubicin (Dox) is a potent chemotherapeutic drug known for its dose-dependent and serious adverse effects, such as cardiotoxicity and myotoxicity. Dox-induced cardiotoxicity (DIC) and muscle toxicity (DIMT) have been studied; however, the mechanisms of Dox-induced apoptosis in soleus muscle are not well defined. Our data shows that with Dox treatment, there is a significant increase in oxidative stress, apoptosis, proapoptotic protein BAX, pPTEN levels, and wnt3a and β-catenin activity (p < 0.05). Moreover, Dox treatment also resulted in decreased antioxidant levels, antiapoptotic BCL2, pAKT, p-mTOR, and endogenous levels of sFRP2 in the soleus muscle tissue (p < 0.05). Secreted frizzled-related protein 2 (sFRP2) treatment attenuated the adverse effects of DIMT and apoptosis in the soleus muscle, evidenced by a decrease in oxidative stress, apoptosis, BAX, pPTEN, and wnt3a and β-catenin activity, as well as an increase in antioxidants, BCL2, pAKT, p-MTOR, and sFRP2 levels (p < 0.05). This data suggests that Dox-induced oxidative stress and apoptosis is mediated through both the Akt-mTOR and wnt/β-catenin pathways. Moreover, the data also shows that sFRP2 modulates these two pathways by increasing signaling of Akt-mTOR and decreased signaling of the wnt/β-catenin pathway. Therefore, our data suggests that sFRP2 has valuable therapeutic potential in reversing Dox-induced oxidative stress and apoptosis in soleus muscle mediated through the Akt-mTOR pathway.

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Section: Discussionsupporting

confidence: 93%

Secreted Frizzled‐Related Protein‐2 Inhibits Doxorubicin‐Induced Apoptosis Mediated through the Akt‐mTOR Pathway in Soleus Muscle

Merino

Singla

2018

Oxidative Medicine and Cellular Longevity

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“…A vacuum was constantly applied to stretch the membrane by 6%, in order to increase membrane stiffness, a condition that preliminary experiments showed to be necessary to allow a proper differentiation of the C2C12 cells into myotubes (data not shown). The following day, at 80% confluence, GM (DMEM with 15% FBS, 4.5 g/L of glucose, 2 mM of L-glutamine, 100 μg/mL of penicillin-streptomycin; Sigma-Aldrich, St. Louis, MO, United States) was replaced with DM containing 2% Horse Serum (HS, Carotenuto et al, 2016). A mixed culture of myoblasts and myotubes was kept for 4 days in DM at 37°C, 5% of CO2 in the Flexcell apparatus, always under constant stretch.…”

Section: Methodsmentioning

confidence: 99%

The Mechanical Stimulation of Myotubes Counteracts the Effects of Tumor-Derived Factors Through the Modulation of the Activin/Follistatin Ratio

et al. 2019

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Activin negatively affects muscle fibers and progenitor cells in aging (sarcopenia) and in chronic diseases characterized by severe muscle wasting (cachexia). High circulating activin levels predict poor survival in cancer patients. However, the relative impact of activin in mediating muscle atrophy and hampered homeostasis is still unknown. To directly assess the involvement of activin, and its physiological inhibitor follistatin, in cancer-induced muscle atrophy, we cultured C2C12 myotubes in the absence or in the presence of a mechanical stretching stimulus and in the absence or presence of C26 tumor-derived factors (CM), so as to mimic the mechanical stimulation of exercise and cancer cachexia, respectively. We found that CM induces activin release by myotubes, further exacerbating the negative effects of tumor-derived factors. In addition, mechanical stimulation is sufficient to counteract the adverse tumor-induced effects on muscle cells, in association with an increased follistatin/activin ratio in the cell culture medium, indicating that myotubes actively release follistatin upon stretching. Recombinant follistatin counteracts tumor effects on myotubes exclusively by rescuing fusion index, suggesting that it is only partially responsible for the stretch-mediated rescue. Therefore, besides activin, other tumor-derived factors may play a significant role in mediating muscle atrophy. In addition to increasing follistatin secretion mechanical stimulation induces additional beneficial responses in myotubes. We propose that in animal models of cancer cachexia and in cancer patients purely mechanical stimuli play an important role in mediating the rescue of the muscle homeostasis reported upon exercise.

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“…We and others have shown that cachexia is characterized by increased inflammatory markers in the skeletal muscle and by satellite cell activation [18,19]. However, in cachexia satellite cells fail to fuse with muscle fibers and their impairment contributes to muscle wasting [20][21][22]. Recently, Cui and al.…”

Section: Introductionmentioning

confidence: 99%

Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation

Daou

Hassani

Matos

et al. 2020

IJMS

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An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic mice, we observed muscle fibers with central nuclei in the absence of molecular markers of bona fide regeneration. These clustered, non-peripheral nuclei were present in NCAM-expressing muscle fibers. Since NCAM expression is upregulated in denervated myofibers, we searched for additional makers of denervation, including AchRs, MUSK, and HDAC. This last one being also consistently upregulated in cachectic muscles, correlated with an increase of central myonuclei. This held true in the musculature of patients suffering from gastrointestinal cancer, where a progressive increase in the number of central myonuclei was observed in weight stable and in cachectic patients, compared to healthy subjects. Based on all of the above, the presence of central myonuclei in cancer patients and animal models of cachexia is consistent with motor neuron loss or NMJ perturbation and could underlie a previously neglected phenomenon of denervation, rather than representing myofiber damage and regeneration in cachexia. Similarly to aging, denervation-dependent myofiber atrophy could contribute to muscle wasting in cancer cachexia.

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α-linolenic acid reduces TNF-induced apoptosis in C2C12 myoblasts by regulating expression of apoptotic proteins

Cited by 34 publications

References 27 publications

Secreted Frizzled‐Related Protein‐2 Inhibits Doxorubicin‐Induced Apoptosis Mediated through the Akt‐mTOR Pathway in Soleus Muscle

Secreted Frizzled‐Related Protein‐2 Inhibits Doxorubicin‐Induced Apoptosis Mediated through the Akt‐mTOR Pathway in Soleus Muscle

The Mechanical Stimulation of Myotubes Counteracts the Effects of Tumor-Derived Factors Through the Modulation of the Activin/Follistatin Ratio

Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation

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