Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G depletion in acute myocardial ischemia

Connolly, Eileen; Thuillier, Vincent; Rouy, Didier; Bouetard, Giséle; Schneider, Robert J.

doi:10.1038/sj.cdd.4401854

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…Loading of the 43S complex onto the mRNA is regulated by the activity of eIF4F (46). This multifactor complex is composed of several proteins, including eIF4E, that directly bind the m 7 GpppX cap structure, eIF4A, which together with eIF4B unwinds secondary structure via its ATP-dependent RNA helicase activity, and eIF4G, which serves as an adaptor protein. eIF4G is the nucleus around which the initiation complex forms, as evidenced by its binding sites not only for eIF4E but also for eIF4A and eIF3 (19).…”

Section: Sepsis-induced Changes In Cap-dependent Translation Initiationmentioning

confidence: 99%

“…eIF4G is pivotal in coordinating peptide-chain initiation, as evidenced by its multiple binding domains for various initiation factors, mRNA, and associated cofactors (19). The function of eIF4G can be inhibited via its proteolytic degradation by proteases (5) and specifically by activation of caspase-3 and calpain I in other stress conditions (7). Of the two isoforms, eIF4GI and eIF4GII, the former is most prominent in muscle.…”

Section: Sepsis-induced Changes In Cap-dependent Translation Initiationmentioning

confidence: 99%

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Regulation of muscle protein synthesis during sepsis and inflammation

Lang

Frost

Vary

2007

American Journal of Physiology-Endocrinology and Metabolism

208

211

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Prolonged sepsis and exposure to an inflammatory milieu decreases muscle protein synthesis and reduces muscle mass. As a result of its ability to integrate diverse signals, including hormones and nutrients, the mammalian target of rapamycin (mTOR) is a dominant regulator in the translational control of protein synthesis. Under postabsorptive conditions, sepsis decreases mTOR kinase activity in muscle, as evidenced by reduced phosphorylation of both eukaryotic initiation factor (eIF)4E-binding protein (BP)-1 and ribosomal S6 kinase (S6K)1. These sepsis-induced changes, along with the redistribution of eIF4E from the active eIF4E·eIF4G complex to the inactive eIF4E·4E-BP1 complex, are preventable by neutralization of tumor necrosis factor (TNF)-α but not by antagonizing glucocorticoid action. Although the ability of mTOR to respond to insulin-like growth factor (IGF)-I is not disrupted by sepsis, the ability of leucine to increase 4E-BP1 and S6K1 phosphorylation is greatly attenuated. This “leucine resistance” results from a cooperative interaction between both TNF-α and glucocorticoids. Finally, although septic animals are not IGF-I resistant, the anabolic actions of IGF-I are nonetheless reduced because of the development of growth hormone resistance, which decreases both circulating and muscle IGF-I. Herein, we highlight recent advances in the mTOR signaling network and emphasize their connection to the atrophic response observed in skeletal muscle during sepsis. Although many unanswered questions remain, understanding the cellular basis of the sepsis-induced decrease in translational activity will contribute to the rational development of therapeutic interventions and thereby minimize the debilitating affects of the atrophic response that impairs patient recovery.

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Section: Sepsis-induced Changes In Cap-dependent Translation Initiationmentioning

confidence: 99%

Section: Sepsis-induced Changes In Cap-dependent Translation Initiationmentioning

confidence: 99%

Regulation of muscle protein synthesis during sepsis and inflammation

Lang

Frost

Vary

2007

American Journal of Physiology-Endocrinology and Metabolism

208

211

View full text Add to dashboard Cite

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“…Rat ischemia model was established by the left anterior descending artery (LAD) ligation as previously described (Connolly et al, 2006; Hu et al, 2009; Wang et al, 2009a). Briefly, after intraperitoneal drug administration, male SD rats were anesthetized and placed in dorsal decubitus supine position and a left thoracotomy was performed at the 5th intercostal space under aseptic surgical conditions.…”

Section: Methodsmentioning

confidence: 99%

Magnesium lithospermate B protects cardiomyocytes from ischemic injury via inhibition of TAB1-p38 apoptosis signaling

Yang

Song

et al. 2010

Front. Pharmacol.

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Danshen has been used in traditional Chinese medicine for hundreds of years to treat cardiovascular diseases. However, its precise cardioprotective components and the underlying mechanism are still unclear. In the present study, we demonstrated that in a rat model of acute myocardial infarction, the treatment with magnesium lithospermate B (MLB), the representative component of phenolic acids in Danshen, significantly reduced the infarct size and the blood lactate dehydrogenase level. In contrast, tanshinone IIA, the representative component of lipophilic tanshinones in Danshen, had no such protective effects. Moreover, in the simulated ischemia cell model, MLB treatment considerably increased the cell viability and reduced the sub-G1 population and the apoptotic nuclei, indicating its anti-apoptotic effect. Further mechanism study revealed that the ischemia-induced p38 phosphorylation was abolished by MLB treatment. Interestingly, MLB specifically inhibited the TGFβ-activated protein kinase 1-binding protein 1 (TAB1) mediated p38 phosphorylation through disrupting the interaction between TAB1 and p38, but it did not affect the mitogen-activated protein kinase 3/6 mediated p38 phosphorylation. In conclusion, the present study identifies MLB as an active component of Danshen in protecting cardiomyocytes from ischemic injury through specific inhibition of TAB1–p38 apoptosis signaling. These results indicate TAB1–p38 interaction as a putative drug target in treating ischemic heart diseases.

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“…Global reduction in protein turnover may mask dramatic changes in specific subsets of proteins. CAP-dependent translation is suppressed by sequestration of eIF4E by its binding protein (4E-BP1) during ischemia [59]. Hypoxia is associated with an increase in translation of mRNAs with an internal ribosomal entry site (IRES) and a decrease of CAP-dependent translation.…”

Section: Mitophagy and Biogenesismentioning

confidence: 99%

Lost in translation: miRNAs and mRNAs in ischemic preconditioning and ischemia/reperfusion injury

Gottlieb

Pourpirali

2016

Journal of Molecular and Cellular Cardiology

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Ischemic stress involves nutrient deprivation, hypoxia, acidosis, and altered levels of various ions and metabolites. Reperfusion, which abruptly alters these parameters, is a second stress to already stressed cells. Ischemic preconditioning, in which brief ischemia alternates with reperfusion to elicit a protective response to ischemia/reperfusion (I/R) injury, revealed the existence of a highly conserved, cell-autonomous, and nearly ubiquitous program. While we often assume that evolutionary selection is irrelevant with respect to myocardial infarctions—which generally occur long after reproduction—the program of ischemia tolerance may date back much further, to hibernating squirrels, turtles, and estivating frogs and snails (extremophiles), which must survive by entering a hypometabolic state. This relationship is further strengthened by the presence of similar signaling pathways and regulatory mechanisms such as mRNA localization and miRNA regulation. These parallels may offer new insights into the myocardial response to I/R injury. This review will explore some of the recent advances in our understanding of autophagy and mitochondrial turnover in the setting of I/R injury, and related findings drawn from research on hibernating extremophiles.

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Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G depletion in acute myocardial ischemia

Cited by 10 publications

References 42 publications

Regulation of muscle protein synthesis during sepsis and inflammation

Regulation of muscle protein synthesis during sepsis and inflammation

Magnesium lithospermate B protects cardiomyocytes from ischemic injury via inhibition of TAB1-p38 apoptosis signaling

Lost in translation: miRNAs and mRNAs in ischemic preconditioning and ischemia/reperfusion injury

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