ABSTRACT
Nutrigenomics in musculoskeletal differentiation:
Resveratrol action on myogenesis process and hypertrophy induction
in C2C12 myoblasts
The new era of nutrition research translates empirical knowledge to evidence-based molecular science, because food components interact with our body at system, organ, cellular and molecular level. Modern nutrition research focuses on promoting health, preventing or delaying the onset of disease, optimizing performance and assessing risk.
Nutrigenomics studies elucidate the ability of bioactive food components to influence gene expression pattern, protein synthesis, degradation and post-translational modifications. Understanding the interrelationship among genome function, cellular metabolism processes and dietary components will enable precise realization of the “Personalized Nutrition” to optimize individual health, diagnosis and nutritional treatment of several chronic diseases, and perhaps increase human longevity.
Regulation of skeletal muscle formation (myogenesis) is essential for normal development as well as to prevent pathological conditions such as muscular dystrophies and inflammatory myopathies.
Skeletal muscle differentiation is a dynamic multistep process that involves two simultaneous phenomena. The first is the induction of muscle-specific genes expression by Myogenic Regulatory Factors (MRFs), such as Myf-5, MyoD, Myf-6 and Myogenin. Second phase is the commitment of myogenic cell into skeletal muscle: mononucleated undifferentiated myoblasts break free from the cell cycle, elongate and fuse into multinucleated myotubes.
Furthermore, cytoskeletal reorganization and severe activation of specific protein kinases represent key regulator mechanisms of skeletal muscle metabolism.
Skeletal muscle hypertrophy can be defined as an overall augmentation in muscle mass, as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by enhanced protein synthesis without an apparent increase in the number of myofibers. Many studies have established that Insulin Like Growth Factor 1 (IGF-1) strongly activates muscle hypertrophy by stimulating the PI3-K/AKT kinases pathway. AKT, in turn, activates the downstream kinase mTOR, which stimulates p70 S6 kinase and other effectors, ultimately culminating in enhancing protein synthesis.
Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, activation of Sirtuins (SIRT1), prevention of mitochondrial disorder, avoidance of obesity-related disease.
In skeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but its action mechanisms and protein targets are not completely known.
To elucidate the underlying mechanism of RSV action, much research has been focused on different tissues and cell types, but less attention has been given to its…
An enzymatic extract produced by Penicillium restrictum having a high level of lipase activity (17.2 U.g -1 ) was obtained by solid-state fermentation using babassu cake as substrate. The enzymatic extract was used in the hydrolysis of a dairy wastewater with high fat contents (180, 450, 900 and 1,200 mg.L -1 ). Different hydrolysis conditions were tested, and it was determined that it should be carried out at a temperature of 35oC, without agitation, with 10% v/v enzymatic extract and a hydrolysis time of 12 hours. Both crude and hydrolysed effluents were then submitted to an anaerobic biological treatment. It was observed that for the enzymatically pretreated effluent there was a significant improvement in the efficiency of the anaerobic treatment. For the highest fat content tested (1,200 mg.L -1 ), removal efficiencies of 19 and 80% were attained for crude and hydrolysed effluents, respectively. In addition, a tenfold increase in the removal rate of COD from the hydrolysed effluent (1.87 kg COD.m -3 .d -1 ) was observed in relation to the crude effluent (0.18 kg COD.m -3 .d -1 ). The results obtained in this study illustrate the viability of using a
The growth characteristics of Gram-negative amidase containing bacteria of Acinetobacter guillouiae llh, Pseudomonas monteilii 5, Alcaligenes faecalis 2 under cultivation in the medium with different concentrations of glucose, sucrose, acetamide and sodium acetate as a carbon were studied. The aim of the work was to optimize the synthetic mineral medium by the source of carbon. It has been determined that the best growth substrate for the manifestation of the amidase activity of the strains was acetamide. With a combination of characteristics such as the biomass yield, the economic coefficient of substrate consumption and enzymatic activity, the optimal acetamide concentration for A. guillouiae llh was 0.025 M, for A faecalis 2 - 0.l M. The growth dynamics of A. faecalis 2 on acetamide in different concentrations was studied. It was shown that the 0.025 M acetamide was insufficient for intensive growth of bacteria, and 0.5 M was inhibitory.
Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by chronic hyperglycaemia mainly explained by insulin resistance and impaired insulin. T2DM is a worldwide increasing disease – in 2013, the International Diabetes Federation estimated that 382 million adults suffered from T2DM and that by 2035 there will be 592 people affected. These worrisome numbers challenge biomedical research at identifying new biomarkers for the diagnosis. The purpose of this study was to analyse and integrate different sources of clinical data with glycomics data in controls, prediabetics and diabetics cohorts, in order to 1) identify the major sources of variation in both data sets, 2) visualize patterns in variables within- and between-omics, 3) determine whether the identified patterns cluster according to known biological sources or conditions, and 5) estimate an aging clock based on the clinical variables and N-glycans and apply it to assess whether the groups of prediabetic and diabetic patients show an accelerated aging as compared with control and between sexes. The analytical methods employed were two-way partial least squares and regression. Results indicate that 1) the phenomics and glycomics joint components are different among groups and sexes over age, 2) intra- and inter-correlations between joint PCs obtained point to a common N-glycan signature (instead of endophenotype-specific), and 3) T2DM patients are biologically older than prediabetics and controls, being this effect more evident for male patients. Our main conclusions are that i) a combination of N-glycans could be used as complementary tool for the early diagnosis of metabolic dysregulation and/or T2D, ii) glycan peaks (GP) 1, GP2, and GP6 are confirmed as markers of aging, while GP8 and GP10 appear associated with dyslipidemia, and iii) this is the first time that prediabetics and diabetics have been included in an aging clock, as pure “healthy” controls do not exist.
The messenger RNA 3’-untranslated region(3’UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3’UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3’UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3’UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3’UTR binding factors and approaches to improve them.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
