IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1

Sacheck, Jennifer M.; Ohtsuka, Akira; McLary, S. Christine; Goldberg, Alfred L.

doi:10.1152/ajpendo.00073.2004

Cited by 536 publications

(507 citation statements)

References 58 publications

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“…This is in contrast with previous literature showing increases of several components of the ubiquitin proteasome system after corticosteroids treatment in in vitro [6,38] and in animal studies [22,39]. To our knowledge, only one in vitro study has demonstrated that treatment of cells (i.e., thymocytes) with dexamethasone decreased proteasome chymotrypsin-like activity in cell extracts [40].…”

Section: Discussioncontrasting

confidence: 88%

“…In skeletal muscle, glucocorticoids decrease the rate of muscle protein synthesis and increase the rate of muscle proteolysis [4]. The stimulatory effect of corticosteroids on muscle proteolysis results from the activation of the proteolytic systems such as the ubiquitin-proteasome system (UPS), the lysosomal system, the calcium-dependent calpain system and the caspase-3 system [5,6]. …”

Section: Introductionmentioning

confidence: 99%

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Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

et al. 2010

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BackgroundHigh dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV)-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids.MethodsRats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP) or 30 mg/kg (high MP) of methylprednisolone.ResultsDiaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only.ConclusionsAdministration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

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Section: Discussioncontrasting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

et al. 2010

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“…This was confirmed by the results shown in Figure 1B where Ang II also stimulated total protein degradation in myotubes, with a parabolic dose -response curve, and with a maximal effect at a concentration of 1 -2.5 mM. Both Ang I and Ang II increased total protein degradation by 30%, which is similar to that induced by glucocorticoids (Sacheck et al, 2004) and PIF (Smith et al, 1999). Protein degradation in myotubes initiated by both Ang I ( Figure 1C) and Ang II ( Figure 1D) was attenuated by the proteasome inhibitors lactacystin (5 mM) and MG132 (10 mM), suggesting that upregulation of the ubiquitinproteasome proteolytic pathway was responsible for the increased protein breakdown.…”

Section: Resultssupporting

confidence: 68%

“…The mechanism by which IGF-I attenuates the increase in proteasome expression induced by Ang II has not been evaluated, but IGF-I has been previously shown to suppress increases in C-2, -3 and -8 proteasome subunit mRNAs in the skeletal muscle of rats treated with dexamethasone as well as mRNAs for ubiquitin and E2 (Chrysis et al, 2002). IGF-I has been shown to suppress protein degradation in myotubes induced by dexamethasone by suppressing expression of two musclespecific ubiquitin ligases (E3s), atrogin-1 and MURF1, which are closely associated with muscle atrophy (Sacheck et al, 2004). Certainly, the mechanism of induction of proteasome expression by Ang II appears to be similar to that of PIF, since the effect of both agonists is attenuated by EPA.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

2005

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The ability of angiotensin I (Ang I) and II (Ang II) to induce directly protein degradation in skeletal muscle has been studied in murine myotubes. Angiotensin I stimulated protein degradation with a parabolic dose -response curve and with a maximal effect between 0.05 and 0.1 mM. The effect was attenuated by coincubation with the angiotensin-converting enzyme (ACE) inhibitor imidaprilat, suggesting that angiotensin I stimulated protein degradation through conversion to Ang II. Angiotensin II also stimulated protein breakdown with a similar dose -response curve, and with a maximal effect between 1 and 2.5 mM. Total protein degradation, induced by both Ang I and Ang II, was attenuated by the proteasome inhibitors lactacystin (5 mM) and MG132 (10 mM), suggesting that the effect was mediated through upregulation of the ubiquitin -proteasome proteolytic pathway. Both Ang I and Ang II stimulated an increased proteasome 'chymotrypsin-like' enzyme activity as well as an increase in protein expression of 20S proteasome a-subunits, the 19S subunits MSS1 and p42, at the same concentrations as those inducing protein degradation. The effect of Ang I was attenuated by imidaprilat, confirming that it arose from conversion to Ang II. These results suggest that Ang II stimulates protein degradation in myotubes through induction of the ubiquitin -proteasome pathway. Protein degradation induced by Ang II was inhibited by insulin-like growth factor and by the polyunsaturated fatty acid, eicosapentaenoic acid. These results suggest that Ang II has the potential to cause muscle atrophy through an increase in protein degradation. The highly lipophilic ACE inhibitor imidapril (Vitort) (30 mg kg À1 ) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model.

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“…19,20) Catabolic hormones (e.g., glucocoricoids) and conditions that interfere with IGF-1 signaling decrease the phosphorylation of FOXO and increase the expression of atrogin-1. 20,24) Our results suggest that insulin stimulates phosphorylation of Akt and FOXO1, resulting in a decrease in atrogin-1 expression during refeeding, and that corticosterone stimulates FOXO1 expression, resulting in an increase in atrogin-1 expression during fasting in skeletal muscle of chicks.…”

mentioning

confidence: 72%

Effects of Fasting and Refeeding on Expression of Atrogin-1 and Akt/FOXO Signaling Pathway in Skeletal Muscle of Chicks

Nakashima

Yakabe

Yamazaki

et al. 2006

Bioscience, Biotechnology, and Biochemistry

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IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1

Abstract: Sacheck, Jennifer M., Akira Ohtsuka, S. Christine McLary, and Alfred L. Goldberg. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab

Cited by 536 publications

References 58 publications

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

Effects of Fasting and Refeeding on Expression of Atrogin-1 and Akt/FOXO Signaling Pathway in Skeletal Muscle of Chicks

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