Contributions of increased efficiency and capacity of protein synthesis to rapid cardiac growth

Morgan, Howard E.; Beinlich, Cathy J.

doi:10.1007/978-1-4615-5765-4_19

Cited by 9 publications

(17 citation statements)

References 36 publications

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“…Circulating EPO may have contributed to myocardial EPO content in these groups, and sustained EPO release may have limited myocardial EPO accumulation following pyruvate treatment. Moreover, messenger RNA abundance is but one of several factors, including translational initiation, translational efficiency, and protein degradation, that determine steady-state tissue contents of specific proteins (24). Furthermore, mRNA synthesis and processing must occur before the encoded protein can be translated, so mRNA abundance may peak before protein content.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass

Ryou¹,

Flaherty²,

Hoxha

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 (HIF-1), an activator of the gene encoding the cardioprotective cytokine erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%, respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also increased ERK phosphorylation by 61 and 118%, respectively, vs. control cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 32% following control CPB vs. sham, but pyruvate cardioplegia prevented these declines, yielding 49 and 80% greater NOS activity and eNOS content vs. respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained activation of EPO's cardioprotective signaling cascade in myocardium.

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Section: Discussionmentioning

confidence: 99%

Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass

Ryou¹,

Flaherty²,

Hoxha

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…In adult cardiac muscle, approximately 85% of the ribosome pool is associated with polysomes, both at steady-state and during periods of hypertrophic growth [6]. This high degree of ribosome occupancy indicates that overall efficiency of protein synthesis is sustained normally at high levels, and that mRNAs compete for ribosomes in order to initiate protein synthesis [17].…”

Section: Discussionmentioning

confidence: 99%

“…Hypertrophy of the myocardium is produced by a global increase in protein synthesis that facilitates accumulation of myofibrils, mitochondria and other primary components of the cardiac muscle cell (cardiocyte) [3,4]. Translational mechanisms play a major role in accelerating the rate of protein synthesis in response to pressure overload by increasing the activity (efficiency) and amount (capacity) of the translation machinery, i.e., ribosomes and associated components such as eukaryotic initiation factors (eIFs) [5,6]. Given that availability of mRNA is not a rate-limiting determinant for protein synthesis, these mechanisms are generally non-selective with respect to translation of individual mRNAs.…”

Section: Introductionmentioning

confidence: 99%

Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload

Spruill¹,

Baicu²,

Zile³

et al. 2008

Journal of Molecular and Cellular Cardiology

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During pressure overload hypertrophy, selective changes in cardiac gene expression occur that regulate growth and modify the structural and functional properties of the myocardium. To determine the role of translational mechanisms, a murine model of transverse aortic constriction was used to screen a set of specified mRNAs for changes in translational activity by measuring incorporation into polysomes in response to acute pressure overload. Candidate mRNAs were selected on the basis of two main criteria: 1) the 5′-untranslated region of the mRNA contains an excessive amount of secondary structure (ΔG < −50 kCal/mol), which is postulated to regulate efficiency of translation, and 2) the protein product has been implicated in the regulation of cardiac hypertrophy. After 24 hours of transverse aortic constriction, homogenates derived from the left ventricle were layered onto 15%-50% linear sucrose gradients and resolved into monosome fractions (messenger ribonucleoprotein particles) and polysome fractions by density gradient ultracentrifugation. The levels of mRNA in each fraction were quantified by real-time RT-PCR. The screen revealed that pressure overload increased translational activity of 6 candidate mRNAs as determined by a significant increase in the percentage of total mRNA incorporated into the polysome fractions. The mRNAs code for several functional classes of proteins linked to cardiac hypertrophy: the transcription factors c-myc, c-jun and MEF2D, growth factors VEGF and FGF-2, and the E3 ubiquitin ligase MDM2. These studies demonstrate that acute pressure overload alters cardiac gene expression by mechanisms that selectively regulate translational activity of specific mRNAs.

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“…The S6 kinases are members of the serine/ threonine protein kinase family and can be divided into two distinct groups, p90 RSK (p90 ribosome S6 protein kinase) and p70 S6K (p70 protein S6 kinase) (1,7). It is known that p90 RSK participates in an important signaling pathway of Ras-Raf-MAPK-p90 RSK -CREB gene transcription (4,14). Antiserum inhibiting tests showed that cell growth was retarded if antibodies inhibited the activities of p90RSKs.…”

mentioning

confidence: 98%

“…These protein kinases are involved in mediating protein synthesis initiation and elongation induced by hormones or growth factors and may play key roles in regulating the rate of protein synthesis during cell proliferation in vivo (7,14,15). The S6 kinases are members of the serine/ threonine protein kinase family and can be divided into two distinct groups, p90 RSK (p90 ribosome S6 protein kinase) and p70 S6K (p70 protein S6 kinase) (1,7).…”

mentioning

confidence: 99%

Cloning, Characterization, and Chromosome Mapping of RPS6KC1, a Novel Putative Member of the Ribosome Protein S6 Kinase Family, to Chromosome 12q12–q13.1

et al. 1999

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Contributions of increased efficiency and capacity of protein synthesis to rapid cardiac growth

Cited by 9 publications

References 36 publications

Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass

Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass

Selective translation of mRNAs in the left ventricular myocardium of the mouse in response to acute pressure overload

Cloning, Characterization, and Chromosome Mapping of RPS6KC1, a Novel Putative Member of the Ribosome Protein S6 Kinase Family, to Chromosome 12q12–q13.1

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