Phosphatidylinositol-3-kinase (PI3K) activity decreases in C2C12 myotubes during acute simulated ischemia at a cost to their survival

Thomas, Mark; Mills, Julia; Engelbrecht, Anna‐Mart

doi:10.1016/j.lfs.2012.06.008

Cited by 5 publications

(9 citation statements)

References 59 publications

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“…P2. Analogous results were seen in other reports where wortmannin or another inhibitor (LY294002) was added to the medium [19,27,28].…”

Section: Accepted Manuscriptsupporting

confidence: 87%

“…Akt (also named protein kinase B) is a serine/threonine kinase, operates downstream of PI3K, and has a key responsibility in regulating signaling pathways concerning cell survival [19,38]. Akt activation prevents muscle atrophy including sarcopenia [39].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of PI3K as well as its primary downstream effector, Akt, is necessary for proliferation and differentiation to occur, and PI3K inhibitors, such as wortmannin and LY294002, are able to block myogenesis [17,18]. Thomas et al [19] determined the role of LY294002 in the PI3K/Akt signaling pathway in C 2 C 12 myotubes and analyzed the related impact on cell death parameters occurring within this context. Their results indicated that simulated ischemia attenuated PI3K activity is associated with decreased Akt-dependent phosphorylation at the level of mTOR and other target proteins.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Milk fat globule membrane protein promotes C2C12 cell proliferation through the PI3K/Akt signaling pathway

et al. 2018

International Journal of Biological Macromolecules

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Milk fat globule membrane (MFGM) protein is known to have several health benefits, including an anti-sarcopenia effect; however, its mechanism is unclear. The aim of this study was to investigate the potential mechanism of action of the MFGM protein. The MFGM protein was extracted and separated into 4 fractions, and Fraction 2 (57% of total MFGM) demonstrated the greatest effect on CC cell proliferation. Milk fat globule-EGF factor 8 (MFG-E8) accounted for 82.35% of the MFGM protein. The effects of whole Fraction 2 (100μg/mL, 200μg/mL and 300μg/mL) on cell proliferation and morphology were measured. Using qRT-PCR or a Western blot assay, several regulatory factors, e.g., PI3K P85α, p-pI3K p85α (Tyr 508), Akt, p-Akt (Ser 473), mTOR and p-mTOR (Ser 2448), were measured in cells incubated with 200μg/mL of Fraction 2 with or without wortmannin. The results demonstrated that Fraction 2 induced CC cell proliferation in a dose-dependent manner, upregulated the mRNA expression of mTOR and p70S6K, and activated PI3K, Akt, mTOR and P70S6K phosphorylation; however, Fraction 2 inhibited FOXO3a and 4E-BP. The results demonstrate that the MFGM protein, predominantly MFG-E8, promotes cell proliferation through the PI3K/Akt/mTOR signaling pathway. This study elucidated the molecular mechanism of the MFGM protein, primarily MFG-E8, in promoting CC cell proliferation via the PI3K/Akt/mTOR/P70S6K signal pathway.

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“…P2. Analogous results were seen in other reports where wortmannin or another inhibitor (LY294002) was added to the medium [19,27,28].…”

Section: Accepted Manuscriptsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Milk fat globule membrane protein promotes C2C12 cell proliferation through the PI3K/Akt signaling pathway

et al. 2018

International Journal of Biological Macromolecules

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“…Thomas et al . have found that the simulated ischaemia is capable of attenuating PI3K activity, which is associated with the inhibition of Akt phosphorylation in C2C12 myotubes . Yen et al .…”

Section: Discussionmentioning

confidence: 97%

Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Chen

Wang

Chan

et al. 2018

J cachexia sarcopenia muscle

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Background Acrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro . The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear. Methods C2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro . Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration. Results Non‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P < 0.05). The protein expression for myogenesis‐related signalling molecules (myogenin and phosphorylated Akt: 0.5 and 1 μM, 85.15% and 51.52% control and 62.63% and 56.57% control, respectively, n = 4, P < 0.05) and myosin heavy chain (MHC: 0.5 and 1 μM, 63.64% and 52.53% control, n = 4, P < 0.05) were decreased in acrolein‐treated myoblasts. Over‐expression of the constitutively active form of Akt in myoblasts during differentiation prevented the inhibitory effects of acrolein (1 μM) on myogenesis (MHC and myogenin protein expression: acrolein with or without constitutively active Akt, 64.65% and 105.21% control and 69.14% and 102.02% control, respectively, n = 5, P < 0.05). Oral administration of acrolein for 4 weeks reduced muscle weights (5 mg/kg/day: 65.52% control, n = 6, P < 0.05) and cross‐sectional area of myofibers in soleus muscles (5 mg/kg/day: 79.92% control, n = 6, P < 0.05) with an up‐regulation of atrogin‐1 and a down‐regulation of phosphorylated Akt protein expressions. Acrolein retarded soleus muscle regeneration in a glycerol‐induced muscle regeneration mouse model (5 mg/kg/day: 49.29% control, n = 4, P < 0.05). Acrolein exposure reduced muscle endurance during rotarod fatigue performance in mice with or without glycerol‐induced muscle injury (5 mg/kg/day without glycerol: 30.43% control, n ...

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“…The phosphorylation of AKT and FoxO is known to be regulated by PI3K (4,41). Therefore, the present study investigated the effects of LY294002, an inhibitor of PI3K.…”

Section: Rg1 Stimulates Pi3k-dependent Phosphorylation Of Akt Andmentioning

confidence: 99%

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

Peng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway. IntroductionMuscle atrophy is characterized by an increase in protein degradation and reduction in protein synthesis. It is associated with a number of human diseases and catabolic conditions, including fasting, disuse, aging, cancer, neuromuscular diseases, stroke, chronic obstructive pulmonary disease, chronic heart failure, HIV-acquired immunodeficiency syndrome and sepsis (1-5). Muscle volume shrinking and muscle weakness induced by muscular dystrophy typically disrupt and adversely affect the life of patients (3,6-8). Therefore, it is essential to understand the mechanism by which skeletal muscle atrophy is regulated.A large amount of protein hydrolysis has previously been identified to occur during muscle atrophy and the ubiquitin-proteasome system (UPS) has been demonstrated to be involved in this process (9)(10)(11)(12)(13)(14). In this system, the proteins are first conjugated into multiple molecules of ubiquitin. The 26S proteasome then recognizes and degrades the ubiquitinated proteins (15,16). Multiple enzymes regulate the protein ubiquitination; these include E1, the ubiquitin-activating enzyme, E2, the ubiquitin conjugating enzyme and E3 ubiquitin ligases (17,18). E3 ubiquitin ligases serve a major role in the specificity of protein degradation, because the specific binding between the protein substrate and E3 occurs prior to the reaction with ubiquitin (18,19).It has been demonstrated that the insulin-signaling pathway is involved in the inhibition of UPS (20). In this pathway, the phosphorylation of insulin receptor substrate is stimulated when insulin binds its receptor. Phosphatidylinositol 3-kinase (PI3K), an intracellular intermediate, is recruited to phosphorylate a serine/threonine kinase, protein kinase B (AKT) during this process. AKT then phosphorylates the forkhead box class O transcription factors, subtype 1 and 3a (FoxO1 and FoxO3a), which pre...

show abstract

Phosphatidylinositol-3-kinase (PI3K) activity decreases in C2C12 myotubes during acute simulated ischemia at a cost to their survival

Cited by 5 publications

References 59 publications

Milk fat globule membrane protein promotes C2C12 cell proliferation through the PI3K/Akt signaling pathway

Milk fat globule membrane protein promotes C2C12 cell proliferation through the PI3K/Akt signaling pathway

Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes

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