1,721,007 research outputs found
The impact of resveratrol and hydrogen peroxide on muscle cell plasticity shows a dose-dependent interaction.
Full text linkWhile reactive oxygen species (ROS) play a role in muscle repair, excessive amounts of ROS for extended periods may lead to oxidative stress. Antioxidants, as resveratrol (RS), may reduce oxidative stress, restore mitochondrial function and promote myogenesis and hypertrophy. However, RS dose-effectiveness for muscle plasticity is unclear. Therefore, we investigated RS dose-response on C2C12 myoblast and myotube plasticity 1. in the presence and 2. absence of different degrees of oxidative stress. Low RS concentration (10 μM) stimulated myoblast cell cycle arrest, migration and sprouting, which were inhibited by higher doses (40-60 μM). RS did not increase oxidative capacity. In contrast, RS induced mitochondria loss, reduced cell viability and ROS production, and activated stress response pathways [Hsp70 and pSer36-p66(ShcA) proteins]. However, the deleterious effects of H2O2 (1000 μM) on cell migration were alleviated after preconditioning with 10 μM-RS. This dose also enhanced cell motility mediated by 100 μM-H2O2, while higher RS-doses augmented the H2O2-induced impaired myoblast regeneration and mitochondrial dehydrogenase activity. In conclusion, low resveratrol doses promoted in vitro muscle regeneration and attenuated the impact of ROS, while high doses augmented the reduced plasticity and metabolism induced by oxidative stress. Thus, the effects of resveratrol depend on its dose and degree of oxidative stress
Overexpression of the elongation factor 1A1 relates to muscle proteolysis and proapoptotic p66(ShcA) gene transcription in hypercatabolic trauma patients.
No full textThe eukaryotic elongation factors (eEF1A2 and eEF1A1) play a key role in translation of messenger RNA (mRNA) to protein. Inskeletal muscle of healthy humans, EEF1A2 is overexpressed and selected over EEF1A1. In cellular stress models, muscle EEF1A1expression increased and was associated with apoptosis and catabolism. We have determined mRNA levels of EEF1A1 and EEF1A2, aswell as those of other proapoptotic genes, such as p66(ShcA) and c-MYC, in skeletal muscle of severely traumatized patients and healthyvolunteers. Muscle protein kinetic was determined by stable isotopes and the arteriovenous technique. The patients were in a hypercataboliccondition because the rate of muscle proteolysis exceeded that of synthesis. Mean mRNA levels of EEF1A1 and EEF1A2 were 165- and29-fold greater (P b .01) in patients than in the control group, respectively. Mean p66(ShcA) mRNA levels were 3-fold greater (P b .05) inpatients than in the controls. In contrast, c-MYC mRNA levels were not significantly different in patients and healthy controls. In patients,muscle mRNA levels of EEF1A1 and p66(ShcA) directly correlated (P b .05) with the rate of proteolysis (R = 0.901 and R = 0.826,respectively). This is in agreement with a reduction in actin and tubulin protein content, both markers of cytoskeletal and sarcomericdisorganization, and with an increased poly(adenosine diphosphate–ribose) polymerase cleavage, a marker of apoptosis. In conclusion, inhypercatabolic traumatized patients, an up-regulation of muscle EEF1A1 and p66(ShcA) relates to proteolysis rate, suggesting aninvolvement of these genes in muscle catabolic response
Decreased IL-10 mRNA expression in patients with advanced renal failure undergoing conservative treatment
No full textChronic renal failure (CRF) is characterized by persistent systemic inflammatory response. We tested the hypothesis that the balance between synthetic capacity of pro-inflammatory, as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and anti-inflammatory cytokines, as IL-10, may become progressively impaired during decline of renal function. Cytokine mRNA transcript levels (fraction of GAPDH mRNA) were detected by real time RT-PCR technique in whole blood cells of patients with far-advanced or less-advanced CRF (glomerular filtration rate lower or greater than 15ml/min per 1.73m(2), respectively) undergoing conservative treatment and in healthy controls. TNF-alpha mRNA levels were greater (p<0.05) in the patients with far-advanced CRF than in those with less-advanced CRF. IL-6 mRNA levels were not significantly different in the two groups. Both groups of patients exhibited greater (p<0.05) TNF-alpha and IL-6 mRNA levels than the healthy controls. IL-10 mRNA levels were greater (p<0.05) in the patients with less-advanced CRF (65+/-18) than in the healthy controls (12+/-2). Nonetheless, in the patients with far-advanced CRF, IL-10 mRNA levels (20+/-10) were lower (p<0.05) than in the patients with less-advanced CRF and not significantly different than in the healthy controls. In conclusion, advanced renal failure is characterized by unbalanced synthetic capacity of pro- and anti-inflammatory cytokines. A progressive decrease in IL-10 synthetic capacity during the course of CRF could contribute to increasing cardiovascular risk
Moderate caloric restriction, but not physiological hyperleptinemia per se, enhances mitochondrial oxidative capacity in rat liver and skeletal muscle--tissue-specific impact on tissue triglyceride content and AKT activation.
No full textThe study aimed at determining, in lean tissues from nonobese rats, whether physiological hyperleptinemia with leptin-induced reduced caloric intake and/or calorie restriction (CR) per se: 1) enhance mitochondrial-energy metabolism gene transcript levels and oxidative capacity; and 2) reduce triglyceride content. Liver and skeletal muscles were collected from 6-month-old Fischer 344 rats after 1-wk leptin sc infusion (0.4 mg/kg . d: leptin + approximately 3-fold leptinemia vs. ad libitum-fed control) or moderate CR (-26% of those fed ad libitum) in pair-fed animals (CR). After 1 wk: 1) leptin and CR comparably enhanced transcriptional expression of mixed muscle mitochondrial genes (P < 0.05 vs. control); 2) CR independently increased (P < 0.05 vs. leptin-control) hepatic mitochondrial-lipooxidative gene expression and oxidative capacity; 3) hepatic but not muscle mitochondrial effects of CR were associated (P < 0.01) with increased activated insulin signaling at AKT level (P < 0.05 vs. leptin-control); 4) liver and muscle triglyceride content were comparable in all groups. In additional experiments, assessing time course of posttranscriptional CR effects, 3-wk superimposable CR (P < 0.05): 1) increased both liver and muscle mitochondrial oxidative capacity; and 2) selectively reduced muscle triglyceride content. Thus, in nonobese adult rat: 1) moderate CR induces early increments of mitochondrial-lipooxidative gene expression and time-dependent increments of oxidative capacity in liver and mixed muscle; 2) sustained moderate CR alters tissue lipid distribution reducing muscle but not liver triglycerides; 3) mitochondrial-lipid metabolism changes are tissue-specifically associated with hepatic AKT activation; 4) short-term physiological hyperleptinemia has no independent stimulatory effects on muscle and liver mitochondrial-lipooxidative gene expression. Increased lean tissue oxidative capacity could favor substrate oxidation over storage during reduced nutrient availability
Epigenetic and miRNAs dysregulation in prostate cancer: the role of nutraceuticals.
No full textThe control of cancer onset and progression is recognized to benefit from specific molecular targeting. MiRNAs are increasingly being implicated in prostate cancer, and the evidence suggests they are possible targets for molecular therapy and diagnosis. In cancer cells, growing attention has been dedicated to novel molecular mechanisms linking the epigenetic scenario to miRNA dysregulation. Currently, the rising evidence shows that nutritional and natural agents, the so-called nutraceuticals, could modulate miRNAs expression, and, as a consequence, might influence cellular responses in health or diseases conditions, including cancer. Among dietary components, plant-derived polyphenols are receiving wide interest, either for their anti-aging and anti-oxidant properties, or for their more general "cell-protective" effects. Above all, their role in preventing the occurrence/recurrence of cancer and, in particular, their potentiality in nutritional intervention for modulating the functions of miRNAs and the epigenetic mechanisms, is still under active debate. This review is focused on the more recent highlights of the impact of miRNAs dysregulation on the onset and progression of prostate cancer, their interplay with epigenetic control and their modulation by natural agents
Regulation of muscle cathepsin B proteolytic activity in protein-depleted patients with chronic diseases.
No full textThe lysosomal cathepsin system contributes to degrading cellular skeletal muscle proteins in many catabolic diseases. We have assessed the relationships between cathepsin B mRNA levels and the enzyme activity for this protease in the skeletal muscle of acutely ill patients with severe trauma (n=7) and in patients with a variety of chronic disease states (hemodialysis, n=3; nervous anorexia, n=1; type 2 diabetes, n=2; prolonged immobilization, n=1).
METHODS:
Muscle biopsies were taken from the vastus lateralis muscle in patients and controls to assess tissue levels of cathepsin B mRNA by competitive-quantitative polymerase chain reaction, cathepsin B proteolytic activity and myofibrillar protein content as alkali-soluble protein to DNA ratio (ASP/DNA). In the trauma patients, muscle protein loss was assessed by the arteriovenous balance technique as rate of phenylalanine release from leg muscle.
RESULTS:
The acute trauma patients exhibited a significant net phenylalanine release from leg muscle (33+/-4 nmol phenylalanine/min/100 ml leg volume) despite a continuous nutritional support. The muscle ASP/DNA ratio was lower (P<0.05) in the patients with chronic diseases (383+/-33) than in groups of healthy controls (554+/-41) or of uncomplicated, moderately obese subjects (525+/-26). Cathepsin B mRNA levels were 6-10 times greater (P<0.05) in the patients with acute trauma or chronic catabolic diseases than in the healthy subjects. Cathepsin B enzymatic activity were 2-3 times greater (P<0.05) in the chronic and acute patients than in the group of uncomplicated, moderately obese subjects. Regression analysis between cathepsin B mRNA and cathepsin B enzymatic activity indicates a significant direct correlation (r=0.84; P<0.05) in the chronic catabolic conditions, but not in the acute trauma patients (r=-0.05).
CONCLUSIONS:
In skeletal muscle of patients with stable chronic catabolic diseases, cathepsin B activity is directly related to cathepsin B mRNA levels, suggesting that in these patients this enzyme could be mainly regulated at the level of gene transcriptio
Vascular sources of oxidative stress: implications for uremia-relatedcardiovascular disease.
No full textChronic oxidative stress that characterizes uremia has potentially devastating effects on the vasculature and has been advocated in the pathogenesis of accelerated atherosclerosis in this disease. Recent advances have been made in our understanding of the molecular mechanisms that regulate expression and activity of key enzymes of vascular oxidative stress (eg, nicotinamide adenine dinucleotide phosphate [NAD{P}H] oxidase) and that dissect their interactions with signalling pathways of inflammation. The finding that NAD(P)H oxidase is upregulated in experimental uremia has important consequences from a physiologic and a therapeutic standpoint. In addition, identification of novel proteins involved in systemic oxidative stress has shed some new light on the pathogenesis of vascular disease. p66(shc) is a cytoplasmic protein that is expressed in a wide range of cell types. Initially believed to be involved in signalling pathways that regulate cell growth and oxidative stress, it has now been shown to play a pivotal role in promoting endothelial dysfunction and atherosclerosis. Although a specific role in uremia-related vascular disease has not yet been shown, available data in humans suggest involvement of p66(shc) in clinical conditions associated with increased oxidative stress
Calorie restriction modulates inactivity-induced changes in the inflammatory markers C-reactive protein and pentraxin-3
No full textCONTEXT:
Energy balance and physical activity potentially influence systemic inflammation.
OBJECTIVE:
Our objective was to test the hypothesis that moderate energy restriction may prevent activation of inactivity-induced inflammatory response.
DESIGN:
Participants were studied four times at the end of 14-d periods of experimental bed rest or controlled ambulation, after receiving eucaloric or hypocaloric diets.
SETTING:
The study was conducted at the clinical research center of the German Space Agency.
SUBJECTS:
Nine healthy young volunteers participated.
INTERVENTIONS:
Energy intake was calibrated to physical activity and decreased by about 20% in hypocaloric conditions.
MAIN OUTCOME MEASURES:
Changes in body fat by dual-energy x-ray absorptiometry as well as plasma inflammatory markers and cytokine mRNA levels in blood cells were measured. Results: Fat mass did not change significantly in eucaloric conditions and decreased in hypocaloric periods (-1.0 +/- 0.3 and -1.0 +/- 0.3 kg in ambulatory and bed rest, respectively). Bed rest in eucaloric conditions increased plasma C-reactive protein (CRP) (+143 +/- 53%) and both the ratios between plasma IL-6 and IL-10 (4+/-1 times) and white blood cell IL-6 and IL-10 mRNAs (5 +/- 1 times). Energy restriction prevented bed-rest-mediated increases in CRP and the IL-6 to IL-10 ratio. Bed rest increased (P = 0.03) long pentraxin-3 (PTX3) plasma concentration, without significant activity-by-diet interaction. In all conditions (n = 36), CRP and PTX3 were inversely correlated (r = -0.61; P < 0.001). Changes in fat mass, leptin, and IL-6 directly correlated with CRP and inversely correlated with PTX3. IL-10 inversely correlated with CRP and directly correlated with PTX3 (r = 0.52; P < 0.01)
- …
