Mechanism of induction of muscle protein degradation by angiotensin II

Russell, Steven T.; Wyke, Stacey M.; Tisdale, Michael J.

doi:10.1016/j.cellsig.2005.09.009

Cited by 69 publications

(50 citation statements)

References 25 publications

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“…Phosphorylation of eIF2a has also been shown to be responsible for the inhibition of protein synthesis in rat liver by vasopressin (Kimball and Jefferson, 1990), and rat skeletal muscle by interleukin-1 (Cooney et al, 1999). Phosphorylation of PKR would also be expected to lead to an increased breakdown of myofibrillar proteins in skeletal muscle by induction of the ubiquitin -proteasome pathway (Wyke and Tisdale, 2005;Russell et al, 2006b) through activation of NF-kB (Zamanian-Daryoush et al, 2000) analogous to the effect of PIF and Ang II .…”

Section: Discussionmentioning

confidence: 99%

“…Mutation of PKR also completely attenuated the induction of protein degradation and upregulation of the ubiquitinproteasome pathway. Induction of the ubiquitin -proteasome pathway by both PIF (Wyke and Tisdale, 2005) and Ang II (Russell et al, 2006b) requires activation of the transcription factor nuclear factor-kB (NF-kB). dsRNA-dependent protein kinase has been shown to activate the upstream kinase IkB kinase (IKK) leading to degradation of the inhibitor protein IkB, leading to release of NF-kB, which migrates to the nucleus and induces transcriptional activation of specific genes (Zamanian-Daryoush et al, 2000).…”

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confidence: 99%

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Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

et al. 2007

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Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the a-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2a have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2a were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2a (correlation coefficient 0.76, P ¼ 0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2a. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2a (correlation coefficient 0.77, P ¼ 0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

et al. 2007

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“…Phosphorylation of eIF2␣ (14) and activation of PKR (15) has been linked to the induction of NF-B transcriptional activity, which in turn is required for the induction of protein degradation by both PIF (7) and Ang II (8), through an increased expression and activity of the ubiquitin-proteasome proteolytic pathway. This suggests a link between the inhibition of protein synthesis and the increase in protein degradation in skeletal muscle in cancer cachexia.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown a role for protein kinase C (PKC) in the induction of proteasome expression by both PIF (43) and Ang II (8). A key step in protein degradation by both PIF and Ang II is the transient formation of reactive oxygen species, possibly through activation of NADPH oxidase by arachidonate and PKC.…”

Section: Discussionmentioning

confidence: 99%

“…Both agents stimulate protein degradation through an increased expression and activity of the ubiquitin-proteasome proteolytic pathway (7,8), by a similar mechanism, involving activation of the nuclear transcription factor NF-B (8,9). For both PIF (7) and Ang II (8) protein degradation is inhibited by specific proteasome inhibitors, while mutations in IB␣, which prevent activation of NF-B and the ubiquitin proteasome pathway (9), also inhibit protein degradation by PIF, confirming a causal relationship. Much less is known about how these agents affect protein synthesis, although with PIF, at least, this has been suggested to arise from an effect on translation efficiency (4).…”

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Skeletal Muscle Atrophy, a Link between Depression of Protein Synthesis and Increase in Degradation

Eley

Tisdale

2007

Journal of Biological Chemistry

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126

137

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Both proteolysis-inducing factor (PIF) and angiotensin II have been shown to produce a depression in protein synthesis in murine myotubes concomitant with an increased phosphorylation of eukaryotic initiation factor 2 (eIF2␣). Both PIF and angiotensin II were shown to induce autophosphorylation of the RNA-dependent protein kinase (PKR), and an inhibitor of this enzyme completely attenuated the depression in protein synthesis and prevented the induction of eIF2␣ phosphorylation. The PKR inhibitor also completely attenuated the increase in protein degradation induced by PIF and angiotensin II and prevented the increase in proteasome expression and activity. To confirm these results myotubes were transfected with plasmids that express either wild-type PKR, or a catalytically inactive PKR variant, PKR⌬6. Myotubes expressing PKR⌬6 showed no increase in eIF2␣ phosphorylation in response to PIF or angiotensin II, no depression in protein synthesis, and no increase in protein degradation or increase in proteasome expression. Induction of the ubiquitin-proteasome pathway by PIF and angiotensin II has been linked to activation of the transcription factor nuclear factor-B (NF-B). Inhibition of PKR prevented nuclear migration of NF-B in response to both PIF and angiotensin II, by preventing degradation of the inhibitor protein I-B. Phosphorylation of PKR and eIF2␣ was also significantly increased in the gastrocnemius muscle of weight losing mice bearing the MAC16 tumor, suggesting that a similar process may be operative in cancer cachexia. These results provide a link between the depression of protein synthesis in skeletal muscle and the increase in protein degradation.

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Role of resveratrol in regulation of cellular defense systems against oxidative stress

2017

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Resveratrol, a natural polyphenolic compound, is found in various kinds of fruits, plants, and their commercial products such as red wine. It has been demonstrated to exhibit a variety of health-promoting effects including prevention and/or treatment of cardiovascular diseases, inflammation, diabetes, neurodegeneration, aging, and cancer. Cellular defensive properties of resveratrol can be explained through its ability of either directly neutralizing reactive oxygen species/reactive nitrogen species (ROS/RNS) or indirectly upregulating the expression of cellular defensive genes. As a direct antioxidant agent, resveratrol scavenges diverse ROS/RNS as well as secondary organic radicals with mechanisms of hydrogen atom transfer and sequential proton loss electron transfer, thereby protecting cellular biomolecules from oxidative damage. Resveratrol also enhances the expression of various antioxidant defensive enzymes such as heme oxygenase 1, catalase, glutathione peroxidase, and superoxide dismutase as well as the induction of glutathione level responsible for maintaining the cellular redox balance. Such defenses could be achieved by regulating various signaling pathways including sirtuin 1, nuclear factor-erythroid 2-related factor 2 and nuclear factor jB. This review provides current understanding and information on the role of resveratrol in cellular defense system against oxidative stress.

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Mechanism of induction of muscle protein degradation by angiotensin II

Cited by 69 publications

References 25 publications

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Skeletal Muscle Atrophy, a Link between Depression of Protein Synthesis and Increase in Degradation

Role of resveratrol in regulation of cellular defense systems against oxidative stress

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