SEARCH · Search PubMed

Results for “mitochondrial quality control”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

245 records · Page 14Linked to original sources

PubMed2004

Mitochondrial function in turkey skeletal muscle--impact on meat quality.

1. M. iliotibialis (MIT) and M. pectoralis (MP) of the BUT Big 6 and Kelly BBB turkey were characterised with respect to physical properties, mitochondrial function, metabolic state, morphology and meat quality. 2. Mitochondrial enzyme activity and respiration rates in MP declined with increasing age while glycolytic enzyme activity remained nearly constant. 3. There were no major differences between BUT Big 6 and Kelly BBB with respect to histological, histochemical or biochemical variables. In spite of the greater adult weight of BUT Big 6, body proportion was equal in both strains. 4. In agreement with the histochemical findings MIT showed higher oxidative capacities, while glycolytic enzyme activity was higher in MP. 5. Pyruvate was the best substrate for oxidative phosphorylation in MIT, but not in MP. Pyruvate dehydrogenase (PDH) activity was up to 15 times less in MP and blood lactate was correlated with intramuscular pH. 6. Turkey breast muscle was restricted in its ability to oxidise pyruvate, especially in those animals that tended to develop intramuscular acidosis post mortem. 7. It is concluded that the in vivo metabolic environment results in acidosis and impaired meat quality, at least in turkey M. pectoralis.

Acidosis↗

PubMed2026

Transcriptomic Insights into Acupuncture Mechanisms in Protecting Ovarian Function in Mice with Premature Ovarian Insufficiency.

OBJECTIVE: To explore the molecular mechanisms underlying the protective effect of acupuncture on ovarian function in mice with cyclophosphamide-induced premature ovarian insufficiency (POI) via transcriptomic analysis. METHODS: Twenty female C57BL/6 mice were divided into 4 groups: control, model, acupuncture, and non-meridian/non-acupoint (NOMA). POI was induced in the model, acupuncture, and non-meridian/non-acupoint groups via cyclophosphamide injection. The acupuncture group received acupuncture at Guanyuan (CV 4), bilateral Guilai (ST 29), and Sanyinjiao (SP 6) for 3 weeks. After the intervention, ovarian tissue weight and ovarian coefficient were calculated, serum levels of key reproductive hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were detected, and ovarian histopathological changes were observed to evaluate ovarian function. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore key functional terms and signaling pathways. Western blot was finally applied to validate the expression of core proteins related to mitochondrial function, endoplasmic reticulum stress and inflammatory pathways. RESULTS: The model group showed reduced ovarian weight and elevated FSH levels. The acupuncture group exhibited significantly higher ovarian weight and coefficient, lower FSH levels, and increased E2 and AMH levels compared to the model group (all P<0.01). Transcriptomic analysis revealed 4,021 DEGs between groups. GO and KEGG analyses revealed that these DEGs were mainly involved in oocyte development, steroid hormone synthesis, and pathways related to mitochondrial function, endoplasmic reticulum stress, and inflammatory signaling. Western blot analysis showed that acupuncture partially restored mitochondrial function markers cytochrome c oxidase subunit IV and NADH dehydrogenase 1 beta subcomplex subunit 8 and reduced endoplasmic reticulum stress markers (glucose-regulated protein 78 and Calnexin, P<0.01). It also downregulated pro-inflammatory proteins (IL-17R, IL-17A, NF-κB p65, p-NF-κB p65, ERK1/2, and p-ERK1/2) and upregulated proteins related to metabolic homeostasis (peroxisome proliferator-activated receptor γ, receptor-interacting protein 140, nicotinamide phosphoribosyltransferase, and sirtuin 1, P<0.01). CONCLUSION: Acupuncture effectively alleviates cyclophosphamide-induced POI in mice, improves ovarian function and follicular quality by regulating cellular functions and inflammatory pathways, suggesting a novel therapeutic approach for POI.

acupuncture↗

PubMedDate not supplied

Intestinal absorption, blood transport and hepatic and muscle metabolism of fatty acids in preruminant and ruminant animals.

Current research on lipid metabolism in ruminants aims to improve the growth and health of the animals and the muscle characteristics associated with meat quality. This review, therefore, focuses on fatty acid (FA) metabolism from absorption to partitioning between tissues and metabolic pathways. In young calves, which were given high-fat milk diets, lipid absorption is delayed because the coagulation of milk caseins results in the retention of dietary fat as an insoluble clot in the abomasum. After weaning, the calves were fed forage- and cereal-based diets containing low levels of long-chain fatty acids (LCFA) but leading to high levels of volatile fatty acid (VFA) production by the rumen microflora. Such differences in dietary FA affect: i) the lipid transport system via the production of lipoproteins by the intestine and the liver, and (ii) the subsequent metabolism of lipids and FA by tissues. In preruminant calves, high-fat feed stimulates the secretion of triacylglycerols (TG)-rich lipoproteins (chylomicrons, very-low density lipoproteins (VLDL)). Diets rich in polyunsaturated FA (PUFA) stimulate the production of chylomicrons by the intestine (at peak lipid absorption) and of high density lipoproteins by the liver, leading to high blood concentrations of cholesterol. High levels of non-esterified FA (NEFA) uptake by the liver in high-yielding dairy cows in early lactation leads to TG infiltration of the hepatocytes (fatty liver). This is due to the low chronic capacity of the liver to synthesise and secrete VLDL particles. This abnormality in hepatic FA metabolism involves defects in apolipoprotein B synthesis and low availability of apolipoproteins and lipids for VLDL packaging. Fatty liver in calves is also caused by milk containing either soybean oil (rich in n-6 PUFA), or coconut oil (rich in C12:0 and C14:0). The ability of muscle tissue to use FA as an energy source depends on its mitochondrial content and, hence, on many physiological factors. The uptake and partitioning of LCFA between oxidation and storage in muscle is regulated by the activity of key intracellular enzymes and binding proteins. One such protein, carnitine palmitoyltransferase I (CPT I) controls the transport of LCFA into mitochondria. Metabolites derived from LCFA inhibit glucose oxidation, decrease the activity of CPT I and decrease the efficiency of ATP production by mitochondria. Most research on tissue lipid metabolism in ruminants is focused on: i) the partitioning of FA oxidation between intracellular peroxisomes and mitochondria in the liver and in muscles; (ii) the regulation of lipid metabolism by leptin, a recently discovered hormone secreted by mature adipocytes; and iii) the effects of activation of the nuclear receptors (PPARs and RXR) by LCFA or by phytol metabolites derived from chlorophyll.

Animals↗

PubMed2006

Effects of hCG as spermiation inducer on European eel semen quality.

Fish sperm quality has traditionally been estimated by subjective evaluation of motility and sperm concentration. Alternative methods for evaluation of sperm quality have been developed in the last decade and enable estimation of spermatozoa head morphometry, membrane integrity and mitochondrial function. Weekly injections of human chorionic gonadotropin (hCG) induced spermiation in farmed male European eels. The milt volume increased from the 5th to 12th weeks. Sperm concentration significantly increased from the 5th week, reaching the highest values at the 8th week, while best motility results were registered at the 9th week of treatment. Coinciding with these intervals, the percentage of dead spermatozoa determined with Hoechst staining showed a reduction in the 8th to 11th weeks of treatment, while the percentage of mitochondrial functionality determined by JC-1 staining did not show a similar pattern. The automatic sperm morphology analysis (ASMA) of the spermatozoa head length, width, area and perimeter showed a significant growth from the 5th to 8th weeks. However, the analysis of isolated descriptive parameters may be difficult to understand because there is a variability in these parameters for each week, making knowledge of the growth kinetic complex. The global size of the spermatozoa head was calculated by applying principal component analysis (PCA), because this method establishes new components that make the interpretation of results easier, allowing a whole interpretation of the changes in the cell morphology. PC1 defines the global head size and shows a significant increase between the 5th and 8th weeks of treatment, showing shorter changes until 12th week. PC2 shows a significant increase in the spermatozoa width from the 5th to 7th weeks. Considering the results of the variations in the principal components defining European eel spermatozoa morphometry, it may be concluded that hCG maturative treatment produced thick cells during the first weeks of spermiation, and subsequent samplings showed an increase in cell width and length. These changes in sperm morphometry coincide with the highest sperm quality assessed as sperm motility and concentration, as well as with the best results obtained in previous studies reporting the best sperm quality between weeks 8 and 10 of hCG treatment. These results support the use of ASMA and Hoechst staining techniques as alternative methods for the evaluation of fish sperm quality.

Animals↗

PubMed2002

The impact of stocking on the genetic integrity of Arctic charr (Salvelinus) populations from the Alpine region.

There is a long tradition of artificially stocking lakes and rivers with fish in the hope to increase the quality and amount of fish that can be harvested. The animals used for stocking often originate in distant hatcheries or hatcheries that breed fish from remote regions. This stocking practice could have effects on the genetic integrity of resident populations. We have analysed here a case of the influence of stocking on Alpine populations of the Arctic charr (usually included into Salvelinus alpinus, but revised to Salvelinus umbla Kottelat 1997) within a unique geographical and historical setting. The Königssee in the Bavarian Alps (Berchtesgaden) was heavily stocked several times during the last century. However, a sample of the ancestral Königssee population still exists in the Grünsee, which lies close to Königssee, but 1000 m higher. To trace the influence of stocking in Königssee we have analysed more than 300 individuals from 10 lake populations, including the source populations of the fish used for stocking. From these we have sequenced a part of the mitochodrial control region and have typed them at six microsatellite loci. The differential distribution of haplotypes, as well as assignment tests, show that the influence of stocking on the genetic integrity of the Königssee population has been negligible. However, our data reveal that in another lake included in our study (Starnberger See), the ancestral population was apparently replaced completely by the populations used for stocking. The major difference between the lakes is the relative preservation of ecological integrity. Königssee was ecologically stable in the past, whereas Starnberger See was heavily polluted at one point, with charr approaching extinction. Interestingly, in a lake neighbouring Starnberger See, the Ammersee, which was also subject to strong pollution but not stocked, the ancestral population has recovered. Our data suggest that the practice of artificial stocking should be reconsidered, or at least monitored for effectiveness.

Animals↗

PubMed2006

REducing Deaths due to OXidative Stress (The REDOXS Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients.

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2 x 2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

Antioxidants↗

PubMed2006

Patagonian wines: implantation of an indigenous strain of Saccharomyces cerevisiae in fermentations conducted in traditional and modern cellars.

In this work we evaluate the implantation capacity of the selected S. cerevisiae indigenous strain MMf9 and the quality of the produced wines in a traditional (T) and a modern (M) cellar with different ecological and technological characteristics in North Patagonia (Argentina). Red musts were fermented in 10,000 l vats using the indigenous strain MMf9 as well as the respective controls: a fermentation conducted with a foreign starter culture (BC strain) in M cellar and a natural fermentation in T cellar. Since commercial S. cerevisiae starters are always used for winemaking in M cellar and in order to compare the results, natural fermentations and fermentations conducted by the indigenous strain MMf9 were performed at pilot (200 l) scale in this cellar, concomitantly. Thirty indigenous yeasts were isolated at three stages of fermentation: initial, middle and end. The identification of the yeast biota associated to vinifications was carried out using ITS1-5.8S-ITS2 PCR-RFLP. The intra-specific variability of the S. cerevisiae populations was evaluated using mtDNA-RFLP analysis. Wines obtained from all fermentations were evaluated for their chemical and volatile composition and for their sensory characteristics. A higher capacity of implantation of the indigenous MMf9 strain was evidenced in the fermentation carried out in M cellar (80% at end stage) than the one carried out in T cellar (40%). This behaviour could indicate that each cellar differs in the diversity of S. cerevisiae strains associated to wine fermentations. Moreover a higher capacity of implantation of the native starter MMf9 with regard to the foreign (BC) one was also found in M cellar. The selected indigenous strain MMf9 was able to compete with the yeast biota naturally present in the must. Additionally, a higher rate of sugar consumption and a lower fermentation temperature were observed in vinifications conducted by MMf9 strain with regard to control fermentations, producing wines with favourable characteristics. Even when its implantation in T fermentation was lower than that observed in M one, we can conclude that the wine features from MMf9 fermentations were better than those from their respective controls. Therefore, MMf9 selected indigenous strain could be an interesting yeast starter culture in North Patagonian wines.

Argentina↗

PubMed1999

Development of beta 3-adrenoceptor agonists for the treatment of obesity and diabetes--an update.

Beta 3-adrenoceptor (beta 3-AR) agonists were found to have remarkable anti-obesity and anti-diabetic effects in rodents shortly after their discovery in the early 1980s. Despite these promising qualities, several pharmaceutical problems and theoretical concerns have slowed the development of these products as therapeutic agents in humans during the last 15 years. To date, the pharmaceutical industry has not been successful in developing a beta 3-AR agonist for use in the treatment of human obesity and type 2 diabetes. Pharmaceutical problems in this area concern important differences between rodent and human beta 3-AR and the difficulty in finding a compound with sufficient bioavailability that is a highly selective and full agonist at the human receptor. Some of these problems seem to have been solved with the cloning of the human beta 3-AR, which has made it possible to develop novel compounds directly and specifically against the human receptor. However, several theoretical concerns still remain. These include the major question as to whether the number of biologically active beta 3-ARs in adult humans is sufficient to produce relevant metabolic effects and, if so, whether their long-term stimulation is safe and free of unwarranted side effects. In addition, the mechanisms of action of beta 3-AR agonists remain poorly understood. Recent studies using CL 316,243, a highly selective beta 3-adrenergic compound, have provided new insights into the potential mechanisms of action of these drugs in rodents as well as the first evidence that treatment with a highly selective beta 3-AR agonist exerts relevant metabolic effects in humans. It appears that chronic beta 3-adrenergic stimulation in white adipose tissue increases the expression of newly discovered mitochondrial uncoupling proteins (UCP 2 and 3) and a "reawakening" of dormant brown adipocytes. In addition, beta 3-ARs may be present in skeletal muscle where ectopic expression of UCP-1 has been reported. If these findings are confirmed, tissues other than brown fat may play an important role in mediating beta 3-adrenergic effects on thermogenesis and substrate oxidation. In humans, treatment with CL 316,243 for 8 weeks, in spite of limited bioavailability, induced marked plasma concentration-dependent increases in insulin sensitivity, lipolysis, and fat oxidation in lean volunteers, without causing beta 1-, or beta 2-mediated side effects. These results clearly indicate that favourable metabolic effects can be achieved by selective beta 3-AR stimulation in humans. The compounds of the next generation currently emerging from preclinical development are full agonists at the human beta 3-AR. These agents have demonstrated promising results in non-human primates. It will be interesting to see whether their efficacy in clinical trials is superior to that achieved with previous (rodent) beta 3-AR agonists and, if so, whether their effects will eventually translate into weight loss and improved metabolic control that could facilitate their use as effective drugs for the treatment of obesity and Type 2 diabetes in humans.

Adrenergic beta-Agonists↗

PubMed1995

Fate and effects of acrolein.

Acrolein is a highly toxic, reactive, and irritating aldehyde that occurs as a product of organic pyrolysis, as a metabolite of a number of compounds, and as a residue in water when used for the control of aquatic organisms. It is an intermediate in the production of acrylic acid, DL-methionine, and numerous other agents. Its major direct use is as a biocide for the control of aquatic flora and fauna. It is introduced to the environment from a variety of sources, including organic combustion such as automobile exhaust, cigarette smoke, and manufacturing and cooking emissions, as well as direct biocidal applications. Organic combustion from both fixed and mobile sources is the significant source of acrolein in the atmosphere; it represents up to 8% of the total aldehydes generated from vehicles and residential fireplaces and 13% of total atmospheric aldehydes. This reactive aldehyde also occurs in organisms as a metabolite of allyl alcohol, allylamine, spermine, spermidine, and the anticancer drug cyclophosphamide, and as a product of UV radiation of the skin lipid triolein. Furthermore, small amounts are found in foods; when animal or vegetable fats are overheated, however, large amounts are produced. Most human contact occurs during exposure to smoke from cigarettes, automobiles, industrial processes, and structural and vegetation fires. Besides cigarette smoke, occupational exposures are a common mode of human contact, particularly in industries that involve combustion of organic compounds. Firefighters, in particular, are exposed to extremely high levels during the extinguishment and overhaul phases of their work. Water may contain significant levels of the herbicide. It has been found in paper mill and municipal effluents at 20-200 micrograms/L, and at 30 micrograms/L as far as 64 km downstream from the point of application. The USEPA-recommended water quality criteria for freshwater are only 1.2 micrograms/L (24-hr avg) and 2.7 micrograms/L (maximum ceiling). Acrolein is highly reactive, and intercompartmental transport is limited. However, it is eliminated from aqueous environments by volatilization and hydration to beta-hydroxypropanal, after which biotransformation occurs, with a half-life of 7-10 d. The Koc for acrolein is 24, and it is not likely to be retained in soil; activated carbon adsorbs only 30% from solution. Thus, the aldehyde is either leached extensively in moist soil or volatilizes quickly from dry soil. It is eliminated from air by reaction with .OH (half-life, 0.5-1.2 d), NOx (half-life, 16 d), and O3 (half-life, 59 d), as well as by photolysis and wet deposition. As expected from its high water solubility, bioaccumulation is low. Acrolein is highly toxic by all routes of exposure. The respiratory system is the most common target: exposure causes localized irritation, respiratory distress, pulmonary edema, cellular necrosis, and increased susceptibility to microbial diseases. Additionally, acute inhalation studies verify that it is a severe respiratory irritant that affects respiratory rates. Respiratory rate depression may have a protective effect by minimizing vapor inhalation, thereby explaining the subadditive effect of acrolein when combined with the other toxic combustion by-products CO and HCHO. Liquid contact with the skin and eyes causes severe irritation, opaque or cloudy corneas, and localized epidermal necrosis, but no allergic contact dermatitis. The cardiovascular system is affected, resulting in increased blood pressure, platelet aggregation, and quick cessation of beating in perfused rat hearts. It may also inhibit mitochondrial oxidative phosphorylation in the myocardium. Acute LD50s and LC50s are low. Levels are 7-46 mg/kg and 18-750 mg/m3, respectively, in rats; aquatic organisms are affected above 11.4 micrograms/L.(ABSTRACT TRUNCATED)

Acrolein↗

PubMed2003

Acetyl-L-carnitine for dementia.

BACKGROUND: Dementia is a common mental health problem affecting 5% of those over 65. Various pathological processes are linked to memory impairment in dementia, particularly those affecting the cholinergic neurotransmitter system. Acetyl-l-carnitine (ALC) is derived from carnitine and is described as having several properties which may be beneficial in dementia. This includes activity at cholinergic neurons, membrane stabilization and enhancing mitochondrial function. Work on the effects of ALC has been ongoing since the 1980s yet the efficacy of ALC in cognitive decline remains unclear. Early studies suggested a beneficial effect of ALC on cognition and behaviour in aging subjects. However, later, larger studies have not supported these findings. Some of the difficulties lie in the early and later studies differing widely in methodology and assessment tools used, and are therefore difficult to compare. ALC is not currently in routine clinical use. OBJECTIVES: The objective of this review is to establish whether Acetyl-l-carnitine is clinically effective in the treatment of people with dementia. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 8 January 2003 using the terms acetyl-l-carnitine, l-carnitine acetyl ester, acetylcarnitine. SELECTION CRITERIA: All double-blind, randomized, trials involving people with dementia in which treatment with ALC was compared with a placebo group DATA COLLECTION AND ANALYSIS: Data were extracted by a reviewer (SH) and entered into Revman 4.1 software. Where possible intention-to-treat data were used, but most of the analyses were of completers (people who completed the study). MAIN RESULTS: There are 11 included trials, all of which had restricted the participants to people with Alzheimer's disease. All trials assessed the cognitive effects of ALC and in addition six considered severity of dementia, six considered functional ability and six considered clinical global impression. There were statistically significant treatment effects in favour of ALC at 12 and 24 weeks for the numbers showing improvement as determined by Clinical Global Impression, [OR 2.33, 95% CI 1.25 to 4.35, P<0.01] and [OR 3.91, 95% CI 1.32 to 11.54, P=0.01] but not as determined by the CIGIC at 52 weeks. There was no evidence of benefit for ALC in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. Various adverse events were reported, but from the meta-analyses there were no statistically significant differences between treated and placebo groups. REVIEWER'S CONCLUSIONS: There is evidence for benefit of ALC on clinical global impression, but there was no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant result may be due to chance. At present there is no evidence to recommend its routine use in clinical practice. Although the intention of the review was to access ALC for the treatment of all dementias, the included trials had confined themselves to participants with Alzheimer's disease. Individual patient data may add to the findings, as would trials including other types of dementia and other outcomes (e.g. mood and caregiver quality of life). However, the evidence does not suggest that ALC is likely to prove an important therapeutic agent. More work on the pharmacokinetics of ALC in humans is also required.

Acetylcarnitine↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗