Insulin-like Growth Factor-I in Muscle Metabolism and Myotherapies

Singleton, J. Robinson; Feldman, Eva L.

doi:10.1006/nbdi.2001.0416

Cited by 59 publications

(41 citation statements)

References 90 publications

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“…However, the maximal CK activity was obtained in PD-treated cells, which indicates extensive cell differentiation over and above that observed with DM or IGF-I treatment. These biochemical findings support the morphological studies where myotube formation was seen in the presence of PD98059 but to a lesser extent in the presence of IGF-I at 48 h. IGF-I is known as a unique proliferation and differentiation promoter of myoblasts (Ewton et al 1994, Florini et al 1996, Coolican et al 1997, Miller et al 2000, Singleton & Feldman 2001. Therefore, the enhanced differentiation (both biochemical and morphological) in the presence of PD98059 versus IGF-I is potentially highly relevant when studying the regulators of enhanced myotube formation.…”

Section: Discussionsupporting

confidence: 84%

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

Al-Shanti

Stewart²

2008

Journal of Endocrinology

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Cell differentiation is usually accompanied by irreversible cell cycle exit, which is a critical step for skeletal muscle differentiation. We therefore hypothesise that PD98059 that blocks the MAP kinase kinase (MEK) pathway (proliferation pathway) when administrated to murine C2 skeletal myoblasts will arrest cell cycle and, consequently, enhances differentiation relative to untreated controls. In this study, we aimed to examine this hypothesis using phenotypic differentiation, biochemical assays, flow cytometry and real-time PCR in C2 cells cultured for 48 h in differentiation media only (untreated) or supplemented with either a single dose of 10 ng/ml IGF-I or 20 mM PD98059 for 48 h. Creatine kinase (CK) activity was increased by 7 . 5-fold (P!0 . 05) in the presence of PD98059, whereas untreated and IGF-I-treated cells induced 4 . 5-and 4-fold increase respectively when compared with baseline controls. Increased CK values in the presence of PD98059 were not only associated with myotube formation but also associated with cell cycle arrest in G1 phase (86G3 . 2%; P!0 . 05). Moreover, the expression of myogenic-specific transcriptional factor mRNAs (MyoD and myogenin) was significantly higher in PD-treated cells (4 . 7G0 . 15 and 314G10 . 2 ng/reaction respectively; P!0 . 05) than untreated (2 . 0G0 . 2 and 233G11 ng/reaction respectively) or IGF-treated cells (3 . 2G0 . 24 and 296G16 . 2 ng/reaction respectively). Unexpectedly, Id3 mRNA, the potent negative regulator of muscle differentiation, was also expressed at significantly higher levels in PD-treated cells (77G0 . 346 ng/reaction; P!0 . 05) than untreated (49G7 . 7 ng/reaction) or IGF-I-treated cells (47G0 . 7 ng/reaction). Furthermore, expression of the muscle differentiation-specific genes (IGF-binding protein-5, IGF-II receptor and IGF-II) was also increased significantly in PD-treated cells when compared with untreated cells. Phosflow analysis showed a significant increase in the levels of phosphorylation of p38 mitogen-activated protein kinase (49 . 0G6 . 7%, P!0 . 05) in PD-treated cells when compared with DM-treated cells (31 . 7G5 . 7%). These findings uncover a previously unconsidered positive effect of PD98059 on C2 myoblast differentiation and identify the pathway(s) underlying PD-induced C2 myoblast differentiation.

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Section: Discussionsupporting

confidence: 84%

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

Al-Shanti

Stewart²

2008

Journal of Endocrinology

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“…6). Although not specifically examined in the present study, increased reducing activity by the Trx system is also likely from metabolic effects of IGF-1 mediated by increased glucose uptake (3,36) and possibly increased NADPH production by the pentose phosphate pathway (3). Thus, we propose that the salient redox effect of IGF-1 on myocytes from MI hearts was an increase in the amount a reduced Trx secondary to increased TrxR activity and supply of NADPH, which promoted the de novo synthesis of Kv4.2 protein (Fig.…”

Section: De-remodeling Of Kv Channels By Igf-1 In Post-mi Heartsmentioning

confidence: 93%

“…Thus, we examined the electrophysiological role of insulin-like growth factor-1 (IGF-1) in the present study since this growth factor has been shown to exert significant antioxidant and antiapoptotic effects on the myocardium (18,36,39,44). As shown in Figure 3A, 10 nM IGF-1 for 4-5 h upregulated I to density in myocytes from MI hearts (filled squares) to a similar extent as JNK=p38 inhibitors.…”

Section: Redox-mediated Remodeling Of K + Channels 27mentioning

confidence: 99%

Role of Apoptosis Signal-Regulating Kinase-1-c-Jun NH₂-Terminal Kinase-p38 Signaling in Voltage-Gated K⁺Channel Remodeling of the Failing Heart: Regulation by Thioredoxin

Tang

Li²,

Zheng

et al. 2011

Antioxidants & Redox Signaling

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Abstractc-Jun NH 2 -terminal kinase ( JNK) and p38 kinase are key regulators of cardiac hypertrophy and apoptosis during pathological stress, but their role in regulating ion channels in the diseased heart is unclear. Thus, we compared the kinase profile and electrophysiological phenotype of the rat ventricle 6-8 weeks after myocardial infarction (MI). Molecular analyses showed that JNK and p38 activities were markedly increased in post-MI hearts, while parallel voltage-clamp studies in ventricular myocytes revealed a characteristic downregulation of transient outward K + current (I to ) density. When post-MI myocytes were treated with JNK or p38 inhibitors, I to density increased to control levels. Upregulation of I to was also elicited by insulin-like growth factor-1, which decreased JNK=p38 activity in post-MI hearts, and these changes were blocked by the thioredoxin (Trx) reductase inhibitor auranofin. Consistent with activation of JNK-p38 signaling, binding of apoptosis signal-regulating kinase-1 with Trx1 was also markedly decreased post-MI, and was reversed by insulin-like growth factor-1 in an auranofinsensitive manner. We conclude that expression of ventricular K + channels is redox regulated and that chronic impairment of the Trx system in the post-MI heart contributes to I to remodeling through sustained activation of apoptosis signal-regulating kinase-1-JNK-p38 signaling. The cardiac Trx system may thus be a novel therapeutic target to reverse or prevent ventricular arrhythmias in the failing heart. Antioxid. Redox Signal. 14, 25-35.

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“…152 Systemic IGF-I and insulin exert an anabolic effect on skeletal muscle and other tissues, primarily owing to an increase in the rate of protein synthesis mediated by mammalian target of rapamycin signaling; however, they also diminish proteolysis a bit by down-regulating some of the muscle-specific ubiquitin ligases that are up-regulated by NF-κB, thereby slowing the muscle proteolysis associated with cancer cachexia. [156][157][158] It is clear that measures that boost plasma levels of free IGF-I and of insulin, such as diets rich in calories and high-quality protein and growth hormone injections, can counteract loss of muscle protein in cachexia to some degree. 159 Conversely, the inanition that often accompanies the cachexia syndrome can exacerbate the inflammationinduced loss of muscle protein through its effects on IGF-I/insulin.…”

mentioning

confidence: 99%

Toward a Core Nutraceutical Program for Cancer Management

McCarty

Block

2006

Integr Cancer Ther

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As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroom β-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, β-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and β-hydroxy-β-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-κB activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

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Insulin-like Growth Factor-I in Muscle Metabolism and Myotherapies

Cited by 59 publications

References 90 publications

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

Role of Apoptosis Signal-Regulating Kinase-1-c-Jun NH₂-Terminal Kinase-p38 Signaling in Voltage-Gated K⁺Channel Remodeling of the Failing Heart: Regulation by Thioredoxin

Toward a Core Nutraceutical Program for Cancer Management

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Insulin-like Growth Factor-I in Muscle Metabolism and Myotherapies

Cited by 59 publications

References 90 publications

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059

Role of Apoptosis Signal-Regulating Kinase-1-c-Jun NH2-Terminal Kinase-p38 Signaling in Voltage-Gated K+Channel Remodeling of the Failing Heart: Regulation by Thioredoxin

Toward a Core Nutraceutical Program for Cancer Management

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Resources

About

Role of Apoptosis Signal-Regulating Kinase-1-c-Jun NH₂-Terminal Kinase-p38 Signaling in Voltage-Gated K⁺Channel Remodeling of the Failing Heart: Regulation by Thioredoxin