Stimulation of left-atrial protein-synthesis rates by increased left-atrial filling pressures in the perfused working rat heart <i>in vitro</i>

Smith, David M.; Sugden, Peter H.

doi:10.1042/bj2160537

Cited by 21 publications

(14 citation statements)

References 27 publications

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“…We have been unable to detect any effect of volume-overload on cardiac protein synthesis [25], although an effect of pressure overload is readily demonstrable [26] in the anterogradely perfused heart. In addition, an increase in pH.…”

Section: Regulation Of Protein Synthesis By Other Factors Co-varying contrasting

confidence: 59%

Correlations between cardiac protein synthesis rates, intracellular pH and the concentrations of creatine metabolites

Sugden

Fuller

1991

Biochemical Journal

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We have examined in detail the correlations between protein synthesis rates, intracellular pH (pHi) and the concentrations of creatine metabolites in the rat heart perfused anterogradely in vitro. Using perfusion buffers ranging from pH 7.2 to 8.2 at 37 degrees C, we were able to manipulate pHi from between 7.24 to 7.66, i.e. from the slightly acidotic to the alkalinotic as compared with the physiological values of pHi (about pH 7.29). The dependence of pHi on extracellular pH (pHo) was linear, with the value of delta pHi/delta pHo being 0.4-0.5. Protein synthesis rates were significantly stimulated when pHi was increased above its physiological value, and they were strongly correlated with pHi. They were also strongly correlated with phosphocreatine concentrations (and with creatine concentrations and phosphocreatine/creatine concentration ratios). Adenine nucleotide (ATP, ADP and AMP) concentrations and the ATP/ADP concentration ratio were not systematically altered by manipulating pHi, and protein synthesis rates showed only a relatively weak dependence on these variables. Since creatine kinase catalyses a reaction that is close to equilibrium in the perfused heart, and since phosphorylation of creatine involves release of a proton, we argue that the changes in phosphocreatine and creatine concentrations are manifestations of alterations in pHi. In this regard, we show that [log[( phosphocreatine]/[creatine]) + log [( ADP]/[ATP])] [the value of which gives [pHi--log (mass action ratio)]] is positively correlated with pHi, although the slope of the line is 0.7, as opposed to the ideal value of unity. We discuss three hypotheses to account for our observations: (i) protein synthesis rates are influenced directly by pHi, (ii) pHi affects the concentrations of creatine metabolites, which in turn affect protein synthesis rates, and (iii) pHi affects the value of an unidentified co-variable, which in turn affects protein synthesis.

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Section: Regulation Of Protein Synthesis By Other Factors Co-varying contrasting

confidence: 59%

Correlations between cardiac protein synthesis rates, intracellular pH and the concentrations of creatine metabolites

Sugden

Fuller

1991

Biochemical Journal

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“…Alteration in cardiac work load may lead to local changes in cellular structures which could be observed in the form of corresponding local alterations in the rate of protein synthesis. This is particularly obvious if increased fibre stretch is the initiating factor in the protein synthesis process, as has been proposed (20,24,32). Morady et al (18) have observed more prominent hypertrophy in the inner layer of the right ventricle of pulmonary artery constricted dogs than in the middle layer, and Anversa et al (1) in the Epi of hypertensive rats than in the Endo.…”

Section: Discussionmentioning

confidence: 86%

Regional glucose uptake and protein synthesis in isolated perfused rat hearts immediately after training and later

et al. 1987

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The effect of 10 weeks of running training and termination of training on the regional distribution of cardiac glucose uptake and protein synthesis were studied in isolated perfused hearts in male rats. The left ventricular glucose uptake in hearts from sedentary rats was 1.87 +/- 0.14 mumol/min per g protein (mean +/- SE), being about 30% higher in the subendocardial than in the subepicardial layer (p less than 0.05). The gradient of left ventricular glucose uptake was similar to the controls in the rats retired from training, but was absent in the trained animals. The altered transmural glucose uptake probably reflects differences in the adaptive response of various myocardial muscle layers to a long-term intermittent increase in cardiac work load. Phenylalanine incorporation was evenly distributed through the left ventricle in all the groups, but was lowered in the left and right ventricles of the trained rats. Phenylalanine incorporation returned to the control level 5 weeks after the cessation of training.

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“…Active systolic tension development has been hypothesized to be a major factor for load-induced protein synthesis in isolated papillary, muscles (10,35). However, passive stretch ofcardiac myocytes or in cardiac muscle preparations has been shown to increase c-fos mRNA levels and stimulate protein synthesis as well (1,9,12,31,36). In the present investigation no increase of c-fos and c-jun mRNA levels was noted in LVs relaxed with BDM over the range of LV balloon volumes used in the experiments to generate graded levels of systolic force.…”

Section: Induction Of C-fos and C-jun Mrna By Systolic Wall Stressmentioning

confidence: 99%

Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts.

Schunkert¹,

Jahn²,

Izumo³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The effect of changes in left ventricular (LV) systolic force generation on cardiac c-fos and c-jun protooncogene expression was studied by using isolated beating hearts from male Wistar rats. An isovolumic buffer-perfused heart preparation was utilized in which coronary flow and heart rate were held constant and increments in LV balloon volume were used to generate defined levels of LV systolic wall stress. Using Northern and slot-blot analyses, we found that LV tissue from control hearts that generated high levels of LV systolic wall stress expressed 3-to 4.4-fold higher c-fos and c-jun mRNA levels in comparison with tissue from the respective flaccid right ventricles, and in comparison with LV tissue from hearts that generated minimal LV systolic wall stress. To distinguish the role of passive LV diastolic wall stretch from active LV force generation, we found that distension of the LV balloon per se did not have a sicant effect on protooncogene induction in hearts perfused with 2,3-butanedone monoime, which prevents systolic cross-bridge cycling and force generation. In additional hearts studied at a constant LV balloon volume to generate an LV end-diastolic pressure of 10 mm Hg, c-fos mRNA levels were proportional to the magnitude fpeak LV systolic wall stress (r = 0.823, P < 0.05). In these protocols, Fos protein was localized by immunohistochemistry in myocyte nuclei with minimal ting in fibroblasts and vascular smooth muscle. When c-fos and c-jun mRNA expression was compared in hearts with chronic LV hypertrophy due to ascending aortic banding and age-matched control hearts that generated similar incremental levels of LV systolic wall stress, sifcantly lower levels of c-fos and c-jun mRNA were measured in the hypertrophied hearts. However, there was no difference in protooncogene mRNA expression in response to stimulation by the Ca2+ ionophore A23187. These data suggest that, in this isolated isovolumic beating heart preparation, the active generation of an acute increment in LV systolic force Independent of passive diastolic myocardlal stretch causes a rapid induction of both c-fos and c-jun, which is down-regulated in the presence of established LV hypertrophy.Myocardial hypertrophy is an adaptive response to pressure overload of the heart that is characterized by protein synthesis (1, 2), changes in isoenzyme expression (3-5), cell growth, and remodeling (6, 7). The hypertrophic process initially appears to normalize the acute elevation of systolic wall stress, whereas in the later stages the capacity to hypertrophy may diminish (7,8). The acute effects of mechanical stimuli on protein synthesis have been documented in isolated myocytes (9), in papillary muscles (10), and in isolated hearts (11, 12). The rapidly induced protooncogenes c-fos, c-jun-and c-myc may play a critical role in mediating the mechanical signals that initiate protein synthesis and cell growth (13-19).We tested the hypothesis that an acute increase in left ventricle (LV) systolic wall stress distinct from passive diastolic...

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Stimulation of left-atrial protein-synthesis rates by increased left-atrial filling pressures in the perfused working rat heart in vitro

Cited by 21 publications

References 27 publications

Correlations between cardiac protein synthesis rates, intracellular pH and the concentrations of creatine metabolites

Correlations between cardiac protein synthesis rates, intracellular pH and the concentrations of creatine metabolites

Regional glucose uptake and protein synthesis in isolated perfused rat hearts immediately after training and later

Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts.

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