Article

Preserved protein synthesis in the heart in response to acute fasting and chronic food restriction despite reductions in liver and skeletal muscle

Department of Nutrition, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
AJP Endocrinology and Metabolism (Impact Factor: 4.09). 08/2008; 295(1):E216-22. DOI: 10.1152/ajpendo.00545.2007
Source: PubMed

ABSTRACT Whole body protein synthesis is reduced during the fed-to-fasted transition and in cases of chronic dietary restriction; however, less is known about tissue-specific alterations. We have assessed the extent to which protein synthesis in cardiac muscle responds to dietary perturbations compared with liver and skeletal muscle by applying a novel (2)H(2)O tracer method to quantify tissue-specific responses of protein synthesis in vivo. We hypothesized that protein synthesis in cardiac muscle would be unaffected by acute fasting or food restriction, whereas protein synthesis in the liver and gastrocnemius muscle would be reduced when there is a protein-energy deficit. We found that, although protein synthesis in liver and gastrocnemius muscle was significantly reduced by acute fasting, there were no changes in protein synthesis in the left ventricle of the heart for either the total protein pool or in isolated mitochondrial or cytosolic compartments. Likewise, a chronic reduction in calorie intake, induced by food restriction, did not affect protein synthesis in the heart, whereas protein synthesis in skeletal muscle and liver was decreased. The later observations are supported by changes in the phosphorylation state of two critical mediators of protein synthesis (4E-BP1 and eIF2alpha) in the respective tissues. We conclude that cardiac protein synthesis is maintained in cases of nutritional perturbations, in strong contrast to liver and gastrocnemius muscle, where protein synthesis is decreased by acute fasting or chronic food restriction.

Download full-text

Full-text

Available from: Yi Li, May 14, 2015
0 Followers
 · 
62 Views
  • Source
    • "Liver and myocardium tissues have different rate of protein synthesis, being higher in hepatocytes, which are able to produce elevated levels of secretory proteins, than in myocardium. However, while the liver can regulate protein synthesis and inhibition according to its own physiological needs and energy demands, the myocardium is resistant to suppression of protein synthesis [35]. The upregulation of the UPR markers along the PERK-eIF2α axis as CHOP, GADD34 and ATF4, although significant, is low when compared with in vitro studies where cell cultures were exposed to anoxia or severe hypoxia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Low oxygen (O2) availability, a condition called hypoxia, has different and profound consequences in tissues and organs. Besides the hypoxia-inducible response, mammalian cells induce a coordinated cytoprotective pathway called Unfolded Protein Response (UPR). We studied the molecular basis of UPR and apoptosis in animal models exposed to different hypoxic stresses and assessed the ability of liver and myocardium to respond to low oxygen by activating different arms of the UPR according to the severity of the insults in a tissue specific manner. We assessed the levels of several UPR markers in hypoxic animals by Real Time PCR and Western blotting. While the hepatocytes activate the apoptotic pathway mediated, in part, by CHOP and p-JNK, we could not detect an UPR-dependent apoptosis in myocytes. Moreover, severe hypoxia results in ATF4 translation, and induction of CHOP and GADD34 transcripts in liver, by contrast in the myocardium, the ATF4-CHOP-GADD34 signaling pathway is not detectably activated. Comparison of several UPR markers in liver and myocardium enabled to underscore the ability of hepatocytes and myocites to selectively activate and fine tune the UPR signaling pathway during hypoxia in vivo.
    Biochimica et Biophysica Acta 03/2012; 1820(7):900-6. DOI:10.1016/j.bbagen.2012.02.016 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The primary objective of this investigation was to determine whether (2)H(2)O and phenylalanine (Phe) flooding dose methods yield comparable fractional rates of protein synthesis (FSR) in skeletal muscle following a single bout of high-intensity resistance exercise (RE). Sprague-Dawley rats were assigned by body mass to either 4-h control (CON 4 h; n = 6), 4-h resistance exercise (RE 4 h; n = 6), 24-h control (CON 24 h; n = 6), or 24-h resistance exercise (RE 24 h; n = 6). The RE groups were operantly conditioned to engage in a single bout of high-intensity, "squat-like" RE. All rats were given an intraperitoneal injection of 99.9% (2)H(2)O and provided 4.0% (2)H(2)O drinking water for either 24 (n = 12) or 4 h (n = 12) prior to receiving a flooding dose of l-[2,3,4,5,6-(3)H]Phe 16 h post-RE. Neither method detected an effect of RE on FSR in the mixed gastrocnemius, plantaris, or soleus muscle. Aside from the qualitative similarities between methods, the 4-h (2)H(2)O FSR measurements, when expressed in percent per hour, were quantitatively greater than the 24-h (2)H(2)O and Phe flooding in all muscles (P < 0.001), and the 24-h (2)H(2)O was greater than the Phe flooding dose in the mixed gastrocnemius and plantaris (P < 0.05). In contrast, the actual percentage of newly synthesized protein was significantly higher in the 24- vs. 4-h (2)H(2)O and Phe flooding dose groups (P < 0.001). These results suggest that the methodologies provide "qualitatively" similar results when a perturbation such as RE is studied. However, due to potential quantitative differences between methods, the experimental question should determine what approach should be used.
    AJP Endocrinology and Metabolism 04/2009; 297(1):E252-9. DOI:10.1152/ajpendo.90872.2008 · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Caloric restriction (CR) is the most robust and reproducible intervention that can extend lifespan in rodents. Studies in invertebrates have led to the identification of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signaling pathway, including DAF-16 (C. elegans) and dFOXO (Drosophila). Mice subjected to CR for 8 weeks showed an increase in FOXO1 mRNA and other longevity-related genes: Gadd 45alpha, glutamine synthase, and catalase in skeletal muscle. To investigate whether FOXO1 expression affects longevity in mammals, transgenic mice were studied that over-express FOXO1 in their skeletal muscle (FOXO1 mice), and in which muscle atrophy occurs. FOXO1 mice showed increases in Gadd 45alpha, and glutamine synthase proteins in skeletal muscle. In FOXO1 mice, the phosphorylation/dephosphorylation state of the p70 S6K and 4E-BP1 proteins were not altered, suggesting that translation initiation of protein synthesis might not be suppressed. The lifespan of FOXO1 mice was similar to their wild-type littermates. FOXO1 overexpression could not prevent aging-induced reduction in catalase, CuZu-SOD, and Mn-SOD mRNA in skeletal muscle. These data suggest that an increase in FOXO1 protein and its activation in skeletal muscle does not extend lifespan in mice.
    Mechanisms of ageing and development 06/2009; 130(7):420-8. DOI:10.1016/j.mad.2009.04.004 · 3.51 Impact Factor
Show more