Control of protein synthesis and ribosome formation in rat heart

Russo, L. A.; Morgan, Howard E.

doi:10.1002/dmr.5610050104

Cited by 13 publications

(12 citation statements)

References 113 publications

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“…However, burn did decrease translational efficiency in cardiac tissue at this time point. The translation of mRNA into protein can be categorized into three stages: initiation, elongation, and termination (8). The decreased protein synthesis observed in striated muscle in response to various catabolic conditions is associated with defects in mRNA translation initiation, the first rate-determining phase of protein synthesis (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Leucine Acutely Reverses Burn-Induced Alterations in Translation Initiation in Heart

Lang

Deshpande

Frost

2004

Shock

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Myocardial dysfunction is a common manifestation of thermal injury, the etiology of which appears to be multifactorial. We have previously demonstrated that burn injury impairs cardiac protein synthesis at the level of translation initiation. The purpose of the present study was to determine whether oral administration of leucine, which is known to stimulate translation initiation in skeletal muscle, can ameliorate burn-induced changes in signal transduction pathways known to regulate protein synthesis in cardiac muscle. To address this aim, thermal injury was produced by a 40% total body surface area full-thickness scald burn in anesthetized rats, and the animals were studied in the fasted condition 24 h later; appropriate time-matched nonburned control rats were also included. Separate groups of control and burn rats also received an oral gavage of leucine. To identify potential mechanisms responsible for regulating mRNA translation in cardiac muscle, several eukaryotic initiation factors (eIFs) were examined using immunoprecipitation and immunoblotting techniques. Hearts from burned rats demonstrated a redistribution of eIF4E as evidenced by the increased binding of the translational repressor 4E-BP1 with eIF4E, a decreased amount of eIF4E bound with eIF4G, and a decreased amount of the hyperphosphorylated gamma-isoform of 4E-BP1. Furthermore, constitutive phosphorylation of mTOR, the ribosomal protein S6, and eIF4G was also decreased in hearts from burned rats. In control rats, leucine failed to alter eIF4E distribution but did increase the phosphorylation of S6K1 and S6. However, in hearts from burn rats, leucine acutely reversed the alterations in eIF4E distribution as well as the changes in S6, eIF4G, and mTOR phosphorylation. These data suggest that oral administration of leucine can acutely reverse multiple defects in cardiac translation initiation produced by thermal injury.

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Section: Introductionmentioning

confidence: 99%

“…Cardiac protein synthesis can be regulated by altering either the number of ribosomes or the efficiency of translation (8).…”

Section: Introductionmentioning

confidence: 99%

Leucine Acutely Reverses Burn-Induced Alterations in Translation Initiation in Heart

Lang

Deshpande

Frost

2004

Shock

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“…The current studies address the hypothesis that burn injury induces specific defects in the regulation of myocardial protein synthesis that are ultimately responsible for at least part of the observed cardiomyopathy. Although alterations in protein balance have been reported for skeletal muscle in response to burn (11), no information exists specifically related to burn-induced change in protein synthesis in the heart.Alterations in cardiac protein synthesis may be caused by changes in either the efficiency of translation or the number of ribosomes (8,46). The translation of mRNA into protein is often divided into three stages: initiation, elongation, and termination (8,43).…”

mentioning

confidence: 99%

“…Alterations in cardiac protein synthesis may be caused by changes in either the efficiency of translation or the number of ribosomes (8,46). The translation of mRNA into protein is often divided into three stages: initiation, elongation, and termination (8,43).…”

mentioning

confidence: 99%

Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation

Lang

Frost

Vary

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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The purpose of the present study was to determine whether burn injury decreases myocardial protein synthesis and potential contributing mechanisms for this impairment. To address this aim, thermal injury was produced by a 40% total body surface area full-thickness scald burn in anesthetized rats, and the animals were studied 24 h late. Burn decreased the in vivo-determined rate of myocardial protein synthesis and translation efficiency by 25% but did not alter the protein synthetic rate in skeletal muscle. To identify potential mechanisms responsible for regulating mRNA translation in cardiac muscle, we examined several eukaryotic initiation factors (eIFs) and elongation factors (eEFs). Burn failed to alter eIF2B activity or the total amount or phosphorylation status of either eIF2 alpha or eIF2B epsilon in heart. In contrast, hearts from burned rats demonstrated 1) an increased binding of the translational repressor 4E-BP1 with eIF4E, 2) a decreased amount of eIF4E associated with eIF4G, and 3) a decreased amount of the hyperphosphorylated gamma-form of 4E-BP1. These changes in eIF4E availability were not seen in gastrocnemius muscle where burn injury did not decrease protein synthesis. Furthermore, constitutive phosphorylation of mTOR, S6K1, the ribosomal protein S6, and eIF4G were also decreased in hearts from burned rats. Burn did not appear to adversely affect elongation because there was no significant difference in the myocardial content of eEF1 alpha or eEF2 or the phosphorylation state of eEF2. The above-mentioned burn-induced changes in mRNA translation were associated with an impairment of in vitro myocardial performance. Finally, 24 h postburn, the cardiac mRNA content of IL-1 beta, IL-6, and high-mobility group protein B1 (but not TNF-alpha) was increased. In summary, these data suggest that thermal injury specifically decreases cardiac protein synthesis in part by decreasing mRNA translation efficiency resulting from an impairment in translation initiation associated with alterations in eIF4E availability and S6K1 activity.

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“…The incidence of developing functional abnormalities 'are greatly increased for individuals with LVH [I]. Cardiac hypertrophy is induced by factors which initially stimulate protein synthesis rates, such as increased aortic pressure [2].…”

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confidence: 99%

The regression of chronic hypertrophy by a calcium channel antagonist and an ACE-inhibitor

Patel

Siddiq

Richardson

et al. 1994

Biochemical Society Transactions

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Hypertension is associated with a variety of morphological changes including left ventricular hypertrophy (LVH). The incidence of developing functional abnormalities 'are greatly increased for individuals with LVH [I]. Cardiac hypertrophy is induced by factors which initially stimulate protein synthesis rates, such as increased aortic pressure [2].Various calcium channel antagonists are currently available, for treating hypertension. However their lack of specificity and pharmacokinetic properties have led to the development of newer compounds. Amlodipine, a novel 1,4-dihydropyridine calcium channel antagonist possesses the desired feature of being administered once daily, due to its slow onset of action and long duration. Its mode of action in modulating cardiac protein synthesis is generally unknown. We therfore investigated (a) ventricular protein composition, and (b) protein synthesis rates, in spontaneously hypertensive rats treated with amlodipine. The effects of amlodipine were also compared with the angiotensin converting enzyme (ACE) inhibitor lisinopril. Male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto ( M Y ) rats were obtained at 15 weeks of age. Rats in the SHR groups had blood pressures within the range 175-190 mmHg. All rats were aged and weight matched from the start of the study. The rats were divided into the following designated groups (1) WKY, (control), treated with ordinary drinking water for 8 weeks.(2) WKY, treated with amlodipine in drinking water for 8 weeks.(3) WKY, treated with lisinopril in drinking water for 8 weeks.(4) SHR. (control), treated with ordinary drinking water for 8 weeks.( 5 ) SHR, treated with amlodipine in drinking water for 8 weeks.(6) SHR, treated with lisinopril in drinking water for 8 weeks.

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Control of protein synthesis and ribosome formation in rat heart

Cited by 13 publications

References 113 publications

Leucine Acutely Reverses Burn-Induced Alterations in Translation Initiation in Heart

Leucine Acutely Reverses Burn-Induced Alterations in Translation Initiation in Heart

Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation

The regression of chronic hypertrophy by a calcium channel antagonist and an ACE-inhibitor

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