Inhibition of C2C12 myotube atrophy by a novel HSP70 inducer, celastrol, via activation of Akt1 and ERK1/2 pathways

Gwag, Taesik; Park, Kyoungsook; Kim, Eun-Jung; Son, Chaeyeon; Junsoo, Park; Nikawa, Takeshi; Choi, Inho

doi:10.1016/j.abb.2013.06.006

Cited by 22 publications

(21 citation statements)

References 45 publications

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“…Treatment of C2C12 myotubes with Dex for 3 h did not affect the levels of phosphorylated and total MEK1/2 and ERK1/2 (Fig. A–E) consistent with a previous study showing Dex had no effect on the signaling pathway (Gwag et al, ). Similarly, heat stress did not alter the levels of phosphorylated and total MEK1/2 and ERK1/2 in Dex‐treated C2C12 myotubes (Fig.…”

Section: Resultssupporting

confidence: 91%

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro

et al. 2016

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It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid‐induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid‐induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel‐like factor 15 (KLF15). Heat stress recovered the dexamethasone‐induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress‐induced protection against glucocorticoid‐induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650–664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.

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Section: Resultssupporting

confidence: 91%

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro

et al. 2016

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“…Their data also showed that heat stress further increased the basically high expression level of HSP70 in soleus muscles. Gwag et al (2013) summarized a potential signaling network in which HSP70 may play an important role in protein synthesis by activating Akt-mTOR signaling. Therefore, it was considered the possibility that the increase in HSP 70 contributes to the activation of Akt by heat stress.…”

Section: Effect Of Heat Stress On Protein Synthesis In Shamoperated Smentioning

confidence: 99%

The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats

et al. 2017

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The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth‐related hypertrophy in sham‐operated muscles and attenuated atrophy in denervated muscles. In denervated muscles, the transcription of ubiquitin ligase, atrogin‐1/muscle atrophy F‐box (Atrogin‐1), and muscle RING‐finger protein‐1 (MuRF‐1), genes was upregulated and ubiquitination of proteins was also increased. Intermittent heat stress inhibited the upregulation of Atrogin‐1, but not MuRF‐1 transcription. And the denervation‐caused reduction in phosphorylated protein kinase B (Akt), 70‐kDa heat‐shock protein (HSP70), and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α), which are negative regulators of Atrogin‐1 and MuRF‐1 transcription, was mitigated. In sham‐operated muscles, repeated application of heat stress did not affect Atrogin‐1 and MuRF‐1 transcription, but increased the level of phosphorylated Akt and HSP70, but not PGC‐1α. Furthermore, the phosphorylation of Akt and ribosomal protein S6, which is known to stimulate protein synthesis, was increased immediately after a single heat stress particularly in the sham‐operated muscles. The effect of a heat stress was suppressed in denervated muscles. These results indicated that the beneficial effects of heat stress on the morphological properties of muscles were brought regardless of innervation. However, the responses of intracellular signaling to heat stress were distinct between the innervated and denervated muscles.

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“…10) In addition, molecular chaperones like heat shock proteins (e.g., HSP72) have been found to play a crucial role in muscle homeostasis via both activation of the Akt1-S6K pathway and suppression of FoxO-ubiquitin-proteasome route. 12,13) T1AM is found in the majority of tissues including serum, brain, heart, skeletal muscle and liver and is produced by deiodination and decarboxylation of thyroxine (T4). 14) This compound is shown to decrease the MR in both in vitro and in vivo models, 5,14) and elicit the most potent hypometabolic effect among several other derivatives of T4 (e.g., T2AM, T3AM, 3′-T1AM).…”

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confidence: 99%

Metabolic Suppression by 3-Iodothyronamine Induced Muscle Cell Atrophy <i>via</i> Activation of FoxO–Proteasome Signaling and Downregulation of Akt1–S6K Signaling

Kim

Chung

Junsoo

et al. 2017

Biological & Pharmaceutical Bulletin

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The homeostasis of muscle properties depends on both physical and metabolic stresses. Whereas physical stress entails metabolic response for muscle homeostasis, the latter does not necessarily involve the former and may thus solely affect the homeostasis. We here report that metabolic suppression by the hypometabolic agent 3-iodothyronamine (T1AM) induced muscle cell atrophy without physical stress. We observed that the oxygen consumption rate of C2C12 myotubes decreased 40% upon treatment with 75 µM T1AM for 6 h versus 10% in the vehicle (dimethyl sulfoxide) control. The T1AM treatment reduced cell diameter of myotubes by 15% compared to the control (p<0.05). The cell diameter was reversed completely by 9 h after T1AM was removed. The T1AM treatment also significantly suppressed the expression levels of heat shock protein 72 and αB-crystallin as well as the phosphorylation levels of Akt1, mammalian target of rapamycin (mTOR), S6K, forkhead box O1 (FoxO1) and FoxO3. In contrast, the levels of ubiquitin E3 ligase MuRF1 and chymotrypsin-like activity of proteasome were significantly elevated by T1AM treatment. These results suggest that T1AM-mediated metabolic suppression induced muscle cell atrophy via activation of catabolic signaling and inhibition of anabolic signaling.

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Inhibition of C2C12 myotube atrophy by a novel HSP70 inducer, celastrol, via activation of Akt1 and ERK1/2 pathways

Cited by 22 publications

References 45 publications

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro

Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro

The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats

Metabolic Suppression by 3-Iodothyronamine Induced Muscle Cell Atrophy <i>via</i> Activation of FoxO–Proteasome Signaling and Downregulation of Akt1–S6K Signaling

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