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Uncoupling Protein (uncoupling + protein)

Distribution by Scientific Domains

Life Sciences	56%
Medical Sciences	18%
Chemistry	18%

Selected Abstracts

Uncoupling protein 2 influences dopamine secretion in PC12h cells

JOURNAL OF NEUROCHEMISTRY, Issue 2 2003
Shigeru Yamada
Abstract Uncoupling protein 2 (UCP2) belongs to the UCP family, and is distributed in many organs including the brain. Although UCP2 is known to be related to many functions such as the regulation of insulin secretion or the scavenging of the radicals, the role of UCP2 in the central nervous system remains unclear. In this report, rat UCP2 (rUCP2) and its mutants were overexpressed in the PC12h cells to determine the physiological roles played by UCP2 in neural cells and to elucidate the mechanisms that regulate these functions. It was found that rUCP2 was activated by the stimulation of the cAMP-protein kinase A (PKA) cascade. Moreover, the activation of rUCP2 suppressed intracellular ATP levels and inhibited the cAMP-dependent increase of dopamine secretion. Thus, UCP2 appears to be regulated by the excitatory stimulus via the cAMP-PKA cascade and serves to negatively control the synaptic output by reducing intracellular ATP levels. [source]

Effect of AOB, a fermented-grain food supplement, on oxidative stress in type 2 diabetic rats

BIOFACTORS, Issue 2 2007
Yukiko Minamiyama
Abstract Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in OLETF rats than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29,33 weeks of diabetic phase in OLETF rats. OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacylgycerol, low density lipoprotein, cholesterol and PAI-1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal. Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator-stimulated phosphoprotein, an index of the NO-cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus. [source]

Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family

FEBS JOURNAL, Issue 9 2000
Benoit Pierrat
Uncoupling proteins (UCPs) are members of the superfamily of the mitochondrial anion carrier proteins (MATP). Localized in the inner membrane of the organelle, they are postulated to be regulators of mitochondrial uncoupling. UCP2 and 3 may play an important role in the regulation of thermogenesis and, thus, on the resting metabolic rate in humans. To identify interacting proteins that may be involved in the regulation of the activity of UCPs, the yeast two-hybrid system was applied. Segments of hUCP2 containing the hydrophilic loops facing the intermembrane space, or combinations of these, were used to screen an adipocyte activation domain (AD) fusion library. The 14.3.3 protein isoforms ,, ,, , were identified as possible interacting partners of hUCP2. Screening of a human skeletal muscle AD fusion library, on the other hand, yielded several clones all of them encoding the , isoform of the 14.3.3 family. Mapping experiments further revealed that all these 14.3.3 proteins interact specifically with the C-terminal intermembrane space domain of both hUCP2 and hUCP3 whereas no interactions could be detected with the C-terminal part of hUCP1. Direct interaction between UCP3 and 14.3.3 , could be demonstrated after in vitro translation by coimmunoprecipitation. When coexpressed in a heterologous yeast system, 14.3.3 proteins potentiated the inhibitory effect of UCP3 overexpression on cell growth. These findings suggest that 14.3.3 proteins could be involved in the targeting of UCPs to the mitochondria. [source]

Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosis

LIVER INTERNATIONAL, Issue 6 2002
Eitaro Taniguchi
Abstract:Background/Aims: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver diseases, this protein may protect liver cells from disease-associated oxidative stress. However, uncoupling protein-2 expression in human liver has not been examined. Methods: We investigated hepatic uncoupling protein-2 distribution in various liver diseases including primary biliary cirrhosis, autoimmune hepatitis, chronic viral hepatitis, and histologically normal liver by immunohistochemistry.Results: Uncoupling protein-2 was expressed in some hepatocytes, however, the degree of hepatocytic uncoupling protein-2 expression did not differ significantly among liver diseases and normal liver. Uncoupling protein-2 was abundant in biliary epithelial cells in primary biliary cirrhosis but not in other liver specimens. Enhanced uncoupling protein-2 expression in biliary epithelial cells was specific for primary biliary cirrhosis and did not result simply from cholestasis. The percentage of uncoupling protein-2 positive bile ducts in primary biliary cirrhosis patients treated with ursodeoxycholic acid was significantly lower than in untreated patients.Conclusions: These results suggest that uncoupling protein-2 is involved in the pathogenesis of primary biliary cirrhosis. [source]

Uncoupling proteins: A complex journey to function discovery

BIOFACTORS, Issue 5 2009
Federica Cioffi
Abstract Since their discovery, uncoupling proteins have aroused great interest due to the crucial importance of energy-dissipating system for cellular physiology. The uncoupling effect and the physiological role of UCP1 (the first-described uncoupling protein) are well established. However, the reactions catalyzed by UCP1 homologues (UCPs), and their physiological roles are still under debate, with the literature containing contrasting results. Current hypothesis propose several physiological functions for novel UCPs, such as: (i) attenuation of reactive oxygen species production and protection against oxidative damage, (ii) thermogenic function, although UCPs do not generally seem to affect thermogenesis, UCP3 can be thermogenic under certain conditions, (iii) involvement in fatty acid handling and/or transport, although recent experimental evidence argues against the previously hypothesized role for UCPs in the export of fatty acid anions, (iv) fatty acid hydroperoxide export, although this function, due to the paucity of the experimental evidence, remains hypothetical, (v) Ca2+ uptake, although results for and against a role in Ca2+ uptake are still emerging, (vi) a signaling role in pancreatic beta cells, where it attenuates glucose-induced insulin secretion. From the above, it is evident that more research will be needed to establish universally accepted functions for UCPs. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]

Pituitary and autonomic responses to cold exposures in man

ACTA PHYSIOLOGICA, Issue 4 2005
J. Leppäluoto
Abstract This review presents hormonal responses to various cold exposures and their calorigenic effects in man and some animals. Previous studies in rats have shown that cold exposures activate the hypothalamic-pituitary-thyroid axis. Increased thyroid hormone concentrations lead to heat production via general stimulation of metabolism (obligatory thermogenesis) and possibly via activation of thyroid hormone receptors and uncoupling protein 1 (UCP 1) and deiodinase enzyme genes in the brown adipose tissue (BAT). In human subjects long-term cold exposures do not seem to activate the pituitary-thyroid axis, but rather accelerate the elimination of triiodothyronine (T3), leading to low serum concentrations of free T3 hormone. In corollary to this a hypothyreotic condition with increased serum thyroid-stimulating hormone and impaired mood and cognitive performance can be observed after long-term cold exposures such as wintering. During cold exposures the sympathetic nerve system is activated and noradrenaline is released to blood circulation and to BAT, where it leads to production of cAMP, lipolysis and free fatty acids. Free fatty acids open the mitochondrial proton channel protein in BAT. Protons enter the mitochondria and inhibit ATP synthesis (uncoupling). By this way energy is transformed into heat (facultatory or adaptive thermogenesis). In adult human subjects the amount of BAT is small and adaptive thermogenesis (non-shivering thermogenesis) has a smaller role. UCP 1 with other uncoupling proteins may have other functions in the control of body weight, sugar balance and formation of reactive oxygen species. [source]

Cold-Induced Recruitment of Brown Adipose Tissue Thermogenesis

EXPERIMENTAL PHYSIOLOGY, Issue 1 2003
Martin Klingenspor
Non-shivering thermogenesis in brown adipose tissue is the main mechanism for thermoregulatory heat production in small mammals and newborns. During cold acclimation the sympathetic innervation triggers the recruitment of brown adipose tissue by hyperplasia, which involves the proliferation and differentiation of precursor cells, and by hypertrophy of mature brown adipocytes. Mitochondrial biogenesis and increased synthesis of the uncoupling protein 1 (UCP-1) are hallmarks of the thermogenic recruitment process. The severalfold increase of mitochondrial protein content during cold acclimation recruits a large capacity for oxidative phosphorylation. However, UCP-1 increases proton leakage across the inner membrane of brown adipocyte mitochondria and thereby dissipates proton motive force as heat instead of ATP synthesis. During recent years considerable progress has been achieved in the analysis of transcriptional mechanisms controlling Ucp1 gene expression. However, so far only little is known about the molecular basis of cold-induced mitochondrial biogenesis in brown adipose tissue. [source]

Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid Secretion

JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2010
A. Mochiduki
Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion. [source]

Differential expression of skeletal muscle proteins in high-fat diet-fed rats in response to capsaicin feeding

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2010
Dong Hyun Kim
Abstract In this study, the effects of capsaicin on expression of skeletal muscle proteins in Sprague,Dawley rats fed with a high-fat diet (HFD) were investigated. Rats were fed a HFD with or without capsaicin treatment for 8,wk. After HFD feeding, capsaicin-treated rats weighed an average of 8% less than those of the HFD control group. Gastrocnemius muscle tissue from lean and obese rats with or without capsaicin treatment was arrayed using 2-DE for detection of HFD-associated markers. Proteomic analysis using 2-DE demonstrated that 36 spots from a total of approximately 600 matched spots showed significantly different expression; 27 spots were identified as gastrocnemius muscle proteins that had been altered in response to capsaicin feeding, and 6 spots could not be identified by mass fingerprinting. Expression of various muscle proteins was determined by immunoblot analysis for the determination of molecular mechanisms, whereby capsaicin caused inhibition of adipogenesis. Immunoblot analysis revealed increased uncoupling protein 3 (UCP3) protein expression in HFD-fed rats, whereas contents were reduced with capsaicin treatment. Compared with the HFD control group, capsaicin treatment increased phosphorylation of AMP-activated protein kinase (AMPIC) CP3 and acetyl-CoA carboxylase (ACC). To support this result, we also analyzed in vitro differential protein expression in L6 skeletal muscle cells. These data suggest that the AMPK-ACC-malonyl-CoA metabolic signaling pathway is one of the targets of capsaicin action. To the best of our knowledge, this is the first proteomic study to report on analysis of diet-induced alterations of protein expression that are essential for energy expenditure in rat muscle. [source]

Gene expression of fatty acid-binding proteins, fatty acid transport proteins (cd36 and FATP) and ,-oxidation-related genes in Atlantic salmon (Salmo salar L.) fed fish oil or vegetable oil

AQUACULTURE NUTRITION, Issue 4 2009
B.E. TORSTENSEN
Abstract Relative gene expression pattern of fatty acid transport proteins (FATP and cd36), intracellular fatty acid-binding proteins (FABP3, FABP10 and FABP11), ,-oxidation-related genes [carnitine palmitoyl transferase II (CPTII), peroxisome proliferator-activated receptor , (PPAR,), acyl-CoA oxidase (AOX), long-chain fatty acyl-CoA synthetase (FACS), acyl-CoA dehydrogenase (dehydrogenase)] and uncoupling protein 2 (UCP2) was assessed by RT-qPCR in Atlantic salmon muscle (red and white), liver, heart, myosepta and visceral fat. FABP11, a FABP isoform not previously described in Atlantic salmon, was highly expressed in visceral fat and myosepta and at the lower level in red muscle, white muscle, myosepta and heart. Furthermore, Atlantic salmon were fed either a diet containing fish oil (FO) or a complete replacement of FO with a vegetable oil blend (55% rapeseed oil, 30% palm oil and 15% linseed oil; VO) for the production cycle (27 months from start of feeding and until ,4.5 kg mean weight). The expression of genes related to ,-oxidation, fatty acid uptake and transport in the white muscle indicate (n = 3) significant down-regulation in VO fed Atlantic salmon and correlated with previously reported white muscle triacylglycerol stores and ,-oxidation. FABP11 in visceral fat and myosepta was also down-regulated in VO fed fish. [source]

Uncoupling proteins: A complex journey to function discovery

Microarray analysis of changes in renal phenotype in the ethylene glycol rat model of urolithiasis: potential and pitfalls

BJU INTERNATIONAL, Issue 4 2004
Daniel H.-C.
OBJECTIVES To investigate, in an initial study, the use of microarray analysis (MA) to develop an information base for urolithiasis. MA enables the screening of thousands of genes simultaneously making it the technique of choice for situations where the results are known, but the underlying mechanisms are not. Little is known about the pathological changes occurring in the kidney during urolithiasis and this has severely hampered efforts to develop effective therapeutics. MATERIALS AND METHODS Male rats were treated with 0.75% ethylene glycol for 2, 4 or 8 weeks; after death the kidneys were processed for RNA isolation and MA, conducted using a rat-based chip (one kidney/chip) and the results confirmed by reverse transcription-polymerase chain reaction (RT-PCR, 21 probe sets; control, four rats; treated, five rats). Targets were defined as different by the software if the fold change (FC) was ,,2, and sorted into functional categories using a data-mining tool. The repeatability of MA was investigated by subjecting the 4-week samples to MA in two independent runs. RESULTS The results for targets with a FC of , 2 were plotted (y = 1.01x , 0.75; r2 0.84). Comparing the results obtained by RT-PCR and MA showed a good qualitative correlation for those targets having a FC of ,,5 as determined by MA. Changes in the expression of genes associated with tubule function and regulation, oxidative damage, and inflammation were the most common in the functional categories. Changes in the expression of tubule-specific markers indicated that there was damage to the proximal (,-adducin, organic anion and cation transporters, sodium-hydrogen exchange protein-isoform 3) and distal tubules (,-adducin, kallikrein) at 2 and 4 weeks. Increased expression of mitochondrial uncoupling protein indicated that there were changes to the mitochondria and oxidative stress at 2 and 4 weeks. CONCLUSION This study shows the power of MA as an exploratory technique, and changes in the expression of several physiologically important genes whose expression has not previously been reported to be affected by hyperoxaluria or calcium oxalate crystalluria. [source]

Pituitary and autonomic responses to cold exposures in man

Ageing, oxidative stress, and mitochondrial uncoupling

ACTA PHYSIOLOGICA, Issue 4 2004
M.-E. Harper
Abstract Mitochondria are a cell's single greatest source of reactive oxygen species. Reactive oxygen species are important for many life sustaining processes of cells and tissues, but they can also induce cell damage and death. If their production and levels within cells is not effectively controlled, then the detrimental effects of oxidative stress can accumulate. Oxidative stress is widely thought to underpin many ageing processes, and the oxidative stress theory of ageing is one of the most widely acknowledged theories of ageing. As well as being the major source of reactive oxygen species, mitochondria are also a major site of oxidative damage. The purpose of this review is a concise and current review of the effects of oxidative stress and ageing on mitochondrial function. Emphasis is placed upon the roles of mitochondrial proton leak, the uncoupling proteins, and the anti-ageing effects of caloric restriction. [source]