Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging is a complex multifactorial process still far from being completely understood. The aim of the present study was to compare the proteome of in vitro cultured dermal fibroblasts from healthy subjects of different ages (i.e. 15 +/- 2, 41 +/- 4 and 82 +/- 3 years old). Proteins of the cell layer were separated by two-dimensional electrophoresis and protein identification was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry; moreover, synthetic gels were qualitatively and quantitatively analyzed by Melanie 3 software. Our study did not reveal any protein typical of any one age group. On the other hand, we observed 38 proteins exhibiting more than three-fold reproducible variations with aging, some (45%) being reduced such as F-actin capping protein alpha1, proteasome subunit alpha type 3, heat shock protein 27, ubiquitin carboxyl-terminal hydrolase isozyme L1, mitochondrial thioredoxin-dependent peroxide reductase, cathepsin B, glutathione S-transferase P, cyclophilin A and calgizzarin. In contrast, T-complex protein 1, probable protein disulfide isomerase ER60, phosphoglycerate kinase 1, Ran-specific GTPase-activating protein, proteasome subunit alpha type 5, triosephosphate isomerase and superoxide dismutase (Mn) increased with age. Furthermore, annexin 1, elongation factor 1beta, proteasome activator complex subunit 1, phosphoglycerate mutase, superoxide dismutase (Cu-Zn) and cofilin, exhibited the highest levels in adult cells; whereas, septin 2 homolog, RNA-binding protein regulatory subunit and ATP synthase D chain revealed the lowest values in adults. The present investigation, underlining the complexity of the aging process, highlights the role of synthetic and degradative pathways in modulating the whole cell machinery and emphasizes that metabolic impairment with age could depend partly on different expression of a number of genes and leading to an imbalance among functional proteins.
...
PMID:Proteome analysis of dermal fibroblasts cultured in vitro from human healthy subjects of different ages. 1283 15

Alterations in a wide array of physiological functions are a normal consequence of aging. Importantly, aged individuals exhibit an enhanced susceptibility to various degenerative diseases and appear less able than their young and adult counterparts to withstand (patho)physiological stress. Elucidation of mechanisms at play in the aging process would benefit the development of effective strategies for enhancing the quality of life for the elderly. It is likely that decrements in cellular and physiological function that occur during aging are the net result of numerous interacting factors. The current review focuses on the potential contribution(s) of free radical-mediated modifications to protein structure/function and alterations in the activities of two major proteolytic systems within cells, lysosomes and the proteasome, to the age-dependent accumulation of fluorescent intracellular granules, termed lipofuscin. Specifically, aging appears to influence the interplay between the occurrences of free radical-derived modifications to protein and the ability of cells to carry out critical proteolytic functions. We present immunochemical and ultrastructural evidence demonstrating the occurrence of a fluorescent protein cross-link derived from free radical-mediated reaction(s) within lipofuscin granules of rat cerebral cortex neurons. In addition, we provide evidence that a fluorophore-modified protein present in lipofuscin granules is the alpha subunit of F1F0-ATP synthase, a mitochondrial protein. It has previously been shown that protein(s) bearing this particular fluorescent cross-link are resistant to proteolysis and can inhibit the proteasome in a non-competitive fashion (J. Biol. Chem. 269 (1994a) 21639; FEBS Lett. 405 (1997) 21). Therefore, the current findings demonstrate that free radical-mediated modifications to protein(s) that lead to the production of inhibitor(s) of cellular proteolytic systems are present on specific protein components of lipofuscin. In addition, the mitochondrial origin of one of these proteins indicates specific intracellular pathways likely to be influenced by free radical events and participate in the formation of lipofuscin. The results of these studies are related to previous in vitro and in vivo observations in the field, thus shedding light on potential consequences to cellular function. In addition, future research directions suggested by the available evidence are discussed.
...
PMID:Aging, lipofuscin formation, and free radical-mediated inhibition of cellular proteolytic systems. 1452 42

ATPases are important molecular machines that convert the chemical energies stored in ATP to mechanical actions within the cell. ATPases are among the most abundant proteins with diverse functions involved in almost every cellular pathway. The well characterised ATPases include the various motor proteins responsible for cargo transfers, cell motilities, and muscle contractions; the protein degradation machinery - the proteasome; the ATP synthase, F-ATPase; and the chaperone systems. Other ATPases include DNA helicases and DNA replication complex; proteins responsible for protein/complex disassembly; and certain gene regulators. It is beyond the scope of this review to cover the complete range of ATPases. Instead, we will focus on a few representative ATPases, chosen based on their diverse mechanisms and properties. Furthermore, this review is by no means trying to cover comprehensively the literature for each ATPase nor the historical aspects in each field. We will focus on describing the various techniques being employed to derive the mechanisms and properties of the chosen ATPases. Among them, high and low resolution structural studies combined with biochemical assays seem to be the dominant technical advances adapted to reveal mechanisms for most of the ATPases except the bacterial sigma54 activators, whose mechanism of action is mostly derived from large amount of biochemical studies. A number of them, especially the F-ATPase and motor proteins, have been studied successfully by various single molecule and imaging techniques. We will therefore discuss them in greater details in order to describe the wide range techniques being utilised.
...
PMID:Mechanisms of ATPases--a multi-disciplinary approach. 1507 20

MURF-1, MURF-2 and MURF-3 are a specific class of RING finger proteins that are expressed in striated muscle tissues. MURF-1 has been suggested to act as an ubiquitin ligase, thereby controlling proteasome-dependent degradation of muscle proteins. Here, we performed yeast two-hybrid (YTH) screens of skeletal muscle cDNA libraries with MURF-1 baits to identify potential myocellular targets of MURF-1-dependent ubiquitination. This identified eight myofibrillar proteins as binding partners of MURF-1: titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin and T-cap. YTH mating studies with MURF-1,2,3 baits indicated that these eight myofibrillar proteins are all targeted redundantly by both MURF-1 and MURF-2. Western blot studies on cardiac tissues from wild-type and MURF-1-deficient mice suggested that titin and nebulin were ubiquitinated at similar levels, and MLC-2 and TnI at reduced levels in MURF-1 KO mice. Mapping of the TnI and titin binding sites on MURF-1 peptide scans demonstrated their binding to motifs highly conserved between MURF-1 and MURF-2. Our data are consistent with a model in which MURF-1 and MURF-2 together target a specific set of myofibrillar proteins redundantly, most likely to control their ubiquitination-dependent degradation. Finally, our YTH screens identified the interaction of MURF-1 with 11 enzymes required for ATP/energy production in muscle including the mitochondrial ATP synthase and cytoplasmic creatine kinase. These data raise the possibility that MURF-1 may coordinately regulate the energy metabolism of mitochondrial and cytoplasmic compartments.
...
PMID:MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination. 1596 62

Using a proteomic approach, we characterized different protein expression profiles in anterior gills of the Chinese mitten crab, Eriocheir sinensis, after cadmium (Cd) exposure. Two experimental conditions were tested: (i) an acute exposure (i.e. 500 microg Cd l(-1) for 3 days) for which physiological, biochemical and ultrastructural damage have been observed previously; (ii) a chronic exposure (i.e. 50 microg Cd l(-1) for 30 days) resulting in physiological acclimation, i.e. increased resistance to a subsequent acute exposure. Two-dimensional gel electrophoresis (2-DE) revealed six protein spots differentially expressed after acute, and 31 after chronic Cd exposure. From these spots, 15 protein species were identified using MS/MS micro-sequencing and MS BLAST database searches. Alpha tubulin, glutathione S-transferase and crustacean calcium-binding protein 23 were down-regulated after an acute exposure, whereas another glutathione S-transferase isoform was up-regulated. Furthermore, analyses revealed the over-expression of protein disulfide isomerase, thioredoxin peroxidase, glutathione S-transferase, a proteasome subunit and cathepsin D after chronic exposure. Under the same condition, ATP synthase beta, alpha tubulin, arginine kinase, glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase were down-regulated. These results demonstrate that acute and chronic exposure to waterborne Cd induced different responses at the protein expression level. Protein identification supports the idea that Cd mainly exerts its toxicity through oxidative stress induction and sulfhydryl-group binding. As a result, analyses showed the up-regulation of several antioxidant enzymes and chaperonins during acclimation process. The gill proteolytic capacity seems also to be increased. On the other hand, the clearly decreased abundance of several enzymes involved in energy transfer suggests that chronic metal exposure induced an important metabolic reshuffling.
...
PMID:Differential protein expression profiles in anterior gills of Eriocheir sinensis during acclimation to cadmium. 1624 38

Angiogenesis controls the new blood supply routes into the tumor mass via the host endothelial cells (ECs). In this study, the EA.hy926 endothelial cell line has been treated with vinblastine (VBL) and rapamycin (RAP), both separately and in combination at low doses. Recently, we demonstrated the synergistic antiangiogenic effects of a combination of VBL and RAP at very low doses in vitro and in vivo. Herein, we confirm the ability of this combined treatment to statistically inhibit the proliferation of ECs, in a synergistic manner, by inducing apoptosis. The aim of this study was to substantiate these findings at the protein level. Differential proteomic analysis was performed on untreated control cells, treated with VBL, incubated with RAP, or subjected to a drug combination. Differentially expressed 113 polypeptide chains were visualized and 65 were identified via MALDI-TOF analysis. Some of the regulated proteins are involved in the processes of angiogenesis, proliferation, migration, and apoptosis. The down-modulation of ATP synthase, annexin A2, heat shock p70, glucose-6-phosphate dehydrogenase, vasodilator-stimulated phosphoprotein, proteasome 26S, tryptophanyl-tRNA synthetase, and stathmin/OP18, as well as the up-modulation of carbonyl reductase, Rho-GDI, and histone H1.0 correlates with the synergistic antiangiogenic activity of VBL and RAP.
...
PMID:Proteomic analysis of anti-angiogenic effects by a combined treatment with vinblastine and rapamycin in an endothelial cell line. 1688 24

The pathogenesis of severe acute respiratory syndrome coronavirus (SARS CoV) is an important issue for treatment and prevention of SARS. Previously, SARS CoV 3C-like protease (3CLpro) has been demonstrated to induce apoptosis via the activation of caspase-3 and caspase-9 (Lin, C. W., Lin, K. H., Hsieh, T. H., Shiu, S. Y. et al., FEMS Immunol. Med. Microbiol. 2006, 46, 375-380). In this study, proteome analysis of the human promonocyte HL-CZ cells expressing SARS CoV 3CLpro was performed using 2-DE and nanoscale capillary LC/ESI quadrupole-TOF MS. Functional classification of identified up-regulated proteins indicated that protein metabolism and modification, particularly in the ubiquitin proteasome pathway, was the main biological process occurring in SARS CoV 3CLpro-expressing cells. Thirty-six percent of identified up-regulated proteins were located in the mitochondria, including apoptosis-inducing factor, ATP synthase beta chain and cytochrome c oxidase. Interestingly, heat shock cognate 71-kDa protein (HSP70), which antagonizes apoptosis-inducing factor was shown to down-regulate and had a 5.29-fold decrease. In addition, confocal image analysis has shown release of mitochondrial apoptogenic apoptosis-inducing factor and cytochrome c into the cytosol. Our results revealed that SARS CoV 3CLpro could be considered to induce mitochondrial-mediated apoptosis. The study provides system-level insights into the interaction of SARS CoV 3CLpro with host cells, which will be helpful in elucidating the molecular basis of SARS CoV pathogenesis.
...
PMID:Proteomic analysis of up-regulated proteins in human promonocyte cells expressing severe acute respiratory syndrome coronavirus 3C-like protease. 1740 83

Efficiency of nutrient utilization is high in neonates with normal birth weights but is reduced in those with intrauterine growth restriction (IUGR). However, the underlying mechanisms are largely unknown. This study was conducted with the piglet model and proteomics technology to test the hypothesis that IUGR affects expression of key proteins that regulate growth and development of the small intestine, liver, and muscle, the major organs involved in the digestion, absorption, and metabolism of dietary nutrients. Jejunum, liver, and gastrocnemius muscle were obtained from IUGR and normal birth-weight piglets at birth for analysis of proteomes using the 2-dimensional-PAGE MS technology. The results indicate that IUGR decreased the levels of proteins that regulate immune function (immunoglobulins and annexin A1), oxidative defense (peroxiredoxin 1, transferrin, and zeta-crystallin), intermediary metabolism (creatine kinase, alcohol dehydrogenase, L-lactate dehydrogenase, prostaglandin F synthase, apolipoprotein AI, catecho O-methyltransferase, and phosphoglycerate kinase 1), protein synthesis (eukaryotic translation initiation factor-3), and tissue growth (beta-actin, desmin, and keratin 10) in a tissue-specific manner. In addition, IUGR increased the levels of proteins that are involved in proteolysis (proteasome alpha-5 and alpha-1 subunits), response to oxidative stress (scavenger-receptor protein and alpha-1 acid glycoprotein), and ATP hydrolysis (F1-ATPase). These novel findings suggest that cellular signaling defects, redox imbalance, reduced protein synthesis, and enhanced proteolysis may be the major mechanisms responsible for abnormal absorption and metabolism of nutrients, as well as reduced growth and impaired development of the small intestine, liver, and muscle in IUGR neonates.
...
PMID:Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs. 1815 5

Although digitalis has been used in clinical treatment extensively, the precise mechanism of its toxic actions on cardiovascular system remained unclear, it would be of interest to study the differential proteomic analysis of vascular endothelial cells in response to toxic concentrations of digitalis thus to provide new agents for treatment of digitalis-induced cytotoxicity. We employed human umbilical vein endothelial cells (HUVEC) as our model system. HUVEC were exposed to increasing concentrations (0.1 nM-10 microM) of digoxin at 12-96 h intervals. Cell viability tests revealed that digoxin played dual effects on cell growth. Apoptosis detection confirmed that apoptosis was primarily responsible for digoxin-induced cell death. Proteomics analysis further revealed that the digoxin-induced apoptosis was accompanied by regulated expression of ATP synthase beta chain, cystatin A, electron transfer flavoprotein, heterogeneous nuclear ribonucleoproteins H3, lamin A, profilin-1, proteasome subunit 5, succinyl-CoA ligase beta chain and heat shock protein 60 (HSP60). Deep study on the overexpression of HSP60 confirmed that HSP60 exerted a protective role in digoxin-induced apoptosis through inhibition of caspase-3 activity in HUVEC. These results provided an impetus for further delineation of mechanism of digoxin-induced cytotoxicity and offered new agents that help attenuate its toxicity.
...
PMID:Comparative proteomics analysis reveals role of heat shock protein 60 in digoxin-induced toxicity in human endothelial cells. 1869 61

Many successful functional studies by gene expression profiling in the literature have led to the perception that profile similarity is likely to imply functional association. But how true is the converse of the above statement? Do functionally associated genes tend to be co-regulated at the transcription level? In this paper, we focus on a set of well-validated yeast protein complexes provided by Munich Information Center for Protein Sequences (MIPS). Using four well-known large-scale microarray expression data sets, we computed the correlations between genes from the same complex. We then analyzed the relationship between the distribution of correlations and the complex size (the number of genes in a protein complex). We found that except for a few large protein complexes, such as mitochondrial ribosomal and cytoplasmic ribosomal proteins, the correlations are on the average not much higher than that from a pair of randomly selected genes. The global impact of large complexes on the expression of other genes in the genome is also studied. Our result also showed that the expression of over 85% of the genes are affected by six large complexes: the cytoplasmic ribosomal complex, mitochondrial ribosomal complex, proteasome complex, F0/F1 ATP synthase (complex V) (size 18), rRNA splicing (size 24) and H+- transporting ATPase, vacular (size 15).
...
PMID:Patterns of co-expression for protein complexes by size in Saccharomyces cerevisiae. 1905 22


1 2 3 4 Next >>

---