Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (-)-Epicatechin, and Betaine.
TL;DR: A review on resveratrol, (-)-epicatechin, and betaine is presented in this article, which summarizes the published data pertaining to their effects on cytochrome c oxidase (COX).
Abstract: Numerous naturally occurring molecules have been studied for their beneficial health effects. Many compounds have received considerable attention for their potential medical uses. Among them, several substances have been found to improve mitochondrial function. This review focuses on resveratrol, (-)-epicatechin, and betaine and summarizes the published data pertaining to their effects on cytochrome c oxidase (COX) which is the terminal enzyme of the mitochondrial electron transport chain and is considered to play an important role in the regulation of mitochondrial respiration. In a variety of experimental model systems, these compounds have been shown to improve mitochondrial biogenesis in addition to increased COX amount and/or its enzymatic activity. Given that they are inexpensive, safe in a wide range of concentrations, and effectively improve mitochondrial and COX function, these compounds could be attractive enough for possible therapeutic or health improvement strategies.
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TL;DR: This review aims to summarize the possible mechanism of resveratrol against pathological cardiac remodeling, in order to provide some help for the in-depth exploration of the mechanism of inhibiting pathological heart remodeling and the development and research of drug targets.
Abstract: Cardiovascular disease is a group of diseases with high mortality in clinic, including hypertension, coronary heart disease, cardiomyopathy, heart valve disease, heart failure, to name a few. In the development of cardiovascular diseases, pathological cardiac remodeling is the most common cardiac pathological change, which often becomes a domino to accelerate the deterioration of the disease. Therefore, inhibiting pathological cardiac remodeling may delay the occurrence and development of cardiovascular diseases and provide patients with greater long-term benefits. Resveratrol is a non-flavonoid polyphenol compound. It mainly exists in grapes, berries, peanuts and red wine, and has cardiovascular protective effects, such as anti-oxidation, inhibiting inflammatory reaction, antithrombotic, dilating blood vessels, inhibiting apoptosis and delaying atherosclerosis. At present, the research of resveratrol has made rich progress. This review aims to summarize the possible mechanism of resveratrol against pathological cardiac remodeling, in order to provide some help for the in-depth exploration of the mechanism of inhibiting pathological cardiac remodeling and the development and research of drug targets.
6 citations
TL;DR: Two weeks of betaine supplementation improved upper- and lower-body muscle endurance and influenced indices of endocrine function following an acute session of high-intensity RE in adolescent handball players.
Abstract: ABSTRACT Objective This study examined the effects of short-term betaine supplementation on muscle endurance, plasma lactate, testosterone and cortisol levels, and the testosterone to cortisol (T/C) ratio in response to acute resistance exercise (RE). Method Using a double-blind, crossover study design, 10 handball players (age ± SD = 16 ± 1 yrs) without prior-structured RE experience performed a high-intensity RE session (leg press followed by bench press; 5 sets to volitional fatigue using 80% baseline 1 repetition maximum (1RM)), before and after 14 days of either placebo (maltodextrin) or betaine (2.5 g·d−1) supplementation. A 30-day washout period separated each treatment. 48 h prior to testing sessions, participants recorded their food intake and did not perform strenuous exercise. Venous blood was sampled before supplementation, and before and after each RE session. Results After betaine supplementation, participants performed more repetitions (p < 0.001) during the leg press (Betaine: 35.8 ± 4.3; Placebo: 24.8 ± 3.6, Cohen’s d = 2.77) and bench press (Betaine: 36.3 ± 2.6; Placebo: 26.1 ± 3.5, Cohen’s d = 3.34). Betaine resulted in lower post-exercise cortisol (Betaine: 7.6 ± 1.7; Placebo: 13 ± 3.4 µg.dL−1, p = 0.003, generalized eta squared (ηG2) = 0.49) and lactate (Betaine: 5.2 ± 0.3; Placebo: 6 ± 0.3 mmol.L−1, p < 0.001, ηG2 = 0.96) and higher total testosterone (Betaine: 15.2 ± 2.2; Placebo: 8.7 ± 1.7 ng.mL−1, p < 0.001, ηG2 = 0.87) and T/C ratio (Betaine: 0.21 ± 0.05; Placebo: 0.07 ± 0.02, p < 0.001, = 0.82). Conclusions Two weeks of betaine supplementation improved upper- and lower-body muscle endurance and influenced indices of endocrine function following an acute session of high-intensity RE in adolescent handball players.
4 citations
TL;DR: In this article , the authors explored the use of deep eutectic solvents (DESs) and DES components as biocompatible nutrient additives for enhancing electroactivity of Bacillus subtilis.
3 citations
TL;DR: A context-dependent vascular response to (–)-epicatechin, a candidate for CVD therapeutic development, is illustrated, leading to improved vasoreactivity in a thermoneutral-derived rat model of vascular dysfunction.
Abstract: Cardiovascular disease (CVD) is a global health concern. Vascular dysfunction is an aspect of CVD, and novel treatments targeting vascular physiology are necessary. In the endothelium, eNOS regulates vasodilation and mitochondrial function; both are disrupted in CVD. (–)-Epicatechin, a botanical compound known for its vasodilatory, eNOS, and mitochondrial-stimulating properties, is a potential therapy in those with CVD. We hypothesized that (–)-epicatechin would support eNOS activity and mitochondrial respiration, leading to improved vasoreactivity in a thermoneutral-derived rat model of vascular dysfunction. We housed Wistar rats at room temperature or in thermoneutral conditions for a total of 16 week and treated them with 1mg/kg body weight (–)-epicatechin for 15 day. Vasoreactivity, eNOS activity, and mitochondrial respiration were measured, in addition to the protein expression of upstream cellular signaling molecules including AMPK and CaMKII. We observed a significant improvement of vasodilation in those housed in thermoneutrality and treated with (–)-epicatechin (p < 0.05), as well as dampened mitochondrial respiration (p < 0.05). AMPK and CaMKIIα and β expression were lessened with (–)-epicatechin treatment in those housed at thermoneutrality (p < 0.05). The opposite was observed with animals housed at room temperature supplemented with (–)-epicatechin. These data illustrate a context-dependent vascular response to (–)-epicatechin, a candidate for CVD therapeutic development.
1 citations
TL;DR: Wang et al. as mentioned in this paper found that Resveratrol (RSV) is one of the most effective natural polyphenols with anti-anxiety and depression effects.
Abstract: Social isolation (SI) is a major risk factor for mood disorders in adolescents. The nucleus accumbens (NAc) is an important reward center implicated in psychiatric disorders. Resveratrol (RSV) is one of the most effective natural polyphenols with anti-anxiety and depression effects. However, little is known about the therapeutic effects and mechanisms of RSV on behavioral abnormality of adolescent social stress. Therefore, this study aimed to investigate the underlying mechanism of RSV on the amelioration of SI-induced behavioral abnormality. We found that SI induced anxiety-like behavior and social dysfunction in isolated female rats. Moreover, SI reduced mitochondrial number and ATP levels and increased thin spine density in the NAc. RNA sequencing results showed that SI changed the transcription pattern in the NAc, including 519 upregulated genes and 610 downregulated genes, especially those related to mitochondrial function. Importantly, RSV ameliorated behavioral and spine abnormalities induced by SI and increased NAc ATP levels and mitochondria number. Furthermore, RSV increased the activity of cytochrome C oxidase (COX) and upregulated mRNA levels of Cox5a, Cox6a1 and Cox7c. These results demonstrate that the modulation of spine plasticity and mitochondrial function in the NAc by RSV has a therapeutic effect on mood disorders induced by social isolation.
1 citations
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TL;DR: It is shown that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice onA standard diet and significantly increases their survival and point to new approaches for treating obesity-related disorders and diseases of ageing.
Abstract: Resveratrol (3,5,49-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-c coactivator 1a (PGC-1a) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.
4,088 citations
TL;DR: RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in P GC-1alpha acetylation and an increase in PGC-1 alpha activity.
3,740 citations
TL;DR: The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
Abstract: In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.
3,572 citations
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.
Abstract: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the agerelated diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.
3,016 citations
TL;DR: Two possible proton pathways for pumping, each spanning from the matrix to the cytosolic surfaces, were identified, including hydrogen bonds, internal cavities likely to contain water molecules, and structures that could form hydrogen bonds with small possible conformational change of amino acid side chains.
Abstract: The crystal structure of bovine heart cytochrome c oxidase at 2.8 A resolution with an R value of 19.9 percent reveals 13 subunits, each different from the other, five phosphatidyl ethanolamines, three phosphatidyl glycerols and two cholates, two hemes A, and three copper, one magnesium, and one zinc. Of 3606 amino acid residues in the dimer, 3560 have been converged to a reasonable structure by refinement. A hydrogen-bonded system, including a propionate of a heme A (heme a), part of peptide backbone, and an imidazole ligand of CuA, could provide an electron transfer pathway between CuA and heme a. Two possible proton pathways for pumping, each spanning from the matrix to the cytosolic surfaces, were identified, including hydrogen bonds, internal cavities likely to contain water molecules, and structures that could form hydrogen bonds with small possible conformational change of amino acid side chains. Possible channels for chemical protons to produce H2O, for removing the produced water, and for O2, respectively, were identified.
2,053 citations