Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria contain a nuclear-encoded heat shock protein, HSP60, which functions as a chaperonin in the post-translational assembly of multimeric proteins encoded by both nuclear and mitochondrial genes. We have isolated and sequenced full-length complementary DNAs coding for this mitochondrial chaperonin in Arabidopsis thaliana and Zea mays. Southern-blot analysis indicates the presence of a single hsp60 gene in the genome of A. thaliana. There is a high degree of homology at the predicted amino acid levels (43 to 60%) between plant HSP60s and their homologues in prokaryotes and other eukaryotes which indicates that these proteins must have similar evolutionarily conserved functions in all organisms. Northern- and western-blot analyses indicate that the expression of the hsp60 gene is developmentally regulated during seed germination. It is also heat-inducible. Developmental regulation of the (beta-subunit of F1-ATPase, an enzyme complex that is involved in the cyanide-sensitive mitochondrial electron transport system, indicates that imbibed embryos undergo rapid mitochondrial biogenesis through the early stages of germination. Based on the functional role of HSP60 in macromolecular assembly, these data collectively suggest that the presence of higher levels of HSP60 is necessary during active mitochondrial biogenesis, when the need for this protein is greatest in assisting the rapid assembly of the oligomeric protein structures.
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PMID:cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin HSP60 and gene expression during seed germination and heat shock. 134 37

A 66 kDa protein, denoted P66, not hitherto classified as an integral component of yeast mitochondrial ATPase, is often observed in preparations of this enzyme complex. A physical association exists between P66 and the assembled ATPase complex since both components are coimmunoprecipitated by anti-F1 beta monoclonal antibody. Two recombinant clones expressing proteins immunologically similar to P66 were isolated from a yeast genomic library in lambda gt11 by screening with a polyclonal anti-holo-ATPase antibody. Based on restriction site mapping and partial nucleotide sequence analysis, both clones encompass the gene encoding the yeast heat shock protein hsp60. The identification of P66 with hsp60, taken together with its demonstrated association with the mitochondrial ATPase complex, is consistent with recent suggestions that hsp60 is involved in assembly of the ATP synthase complex.
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PMID:Identification of a 66 KDa protein associated with yeast mitochondrial ATP synthase as heat shock protein hsp60. 214 85

Hypothermia is known to protect myocardium during ischemia, but its role in induction of a protective stress response before ischemia has not been evaluated. As cold incites stress responses in other tissues, including heat shock protein induction and signaling mitochondrial biogenesis, we postulated that hypothermia in perfused hearts would produce similar phenomena while reducing injury during subsequent ischemia. Studies were performed in isolated perfused rabbit hearts (n = 77): a control group (C) and a hypothermic group (H) subjected to decreasing infusate temperature from 37 to 31 degrees C over 20 min. Subsequent ischemia during cardioplegic arrest at 34 degrees C for 120 min was followed by reperfusion. At 15 min of reperfusion, recovery of left ventricular developed pressure (LVDP), maximum first derivative of left ventricular pressure (LV dP/dtmax), LV -dP/dtmax, and the product of heart rate and LVDP was significantly increased in H (P < 0.01) compared with C hearts. Ischemic contracture started later in H (97.5 +/- 3.6 min) than in C (67.3 +/- 3.3 min) hearts. Myocardial ATP preservation and repletion during ischemia and reperfusion were higher in H than in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine nucleotide translocase isoform 1 (ANT1) and beta-F1-adenosine-triphosphatase (beta-F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved in H hearts after reperfusion. Inducible heat shock protein (HSP70-1) mRNA was elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These data indicate that hypothermia preserves myocardial function and ATP stores during subsequent ischemia and reperfusion. Signaling for mitochondrial biogenesis indexed by ANT1 and beta-F1-ATPase mRNA levels is also preserved during a marked increase in HSP70-1 mRNA.
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PMID:Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia. 953 Jan 89

Temperature modulates both myocardial energy requirements and production. We have previously demonstrated that myocardial protection induced by hypothermic adaptation preserves expression of genes regulating heat shock protein and the nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This preservation is associated with a reduction in ATP depletion similar to that noted in cardioplegic arrested hearts preserved at a critical temperature (30 degrees C) or below. We tested the hypothesis that expression of these genes may also be subject to this temperature threshold phenomenon. Isolated perfused rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34 degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after 45 min of reperfusion. Cardiac function was significantly depressed in the 34 degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4 and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to similar levels at all three temperatures. These results indicate that mRNA expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern consistent with the temperature threshold phenomenon. HSP70-1 expression is not influenced by ischemic temperature. Preservation of gene expression for these mitochondrial proteins implies that signaling for mitochondrial biogenesis or resynthesis is maintained after ischemic insult.
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PMID:Temperature threshold and preservation of signaling for mitochondrial membrane proteins during ischemia in rabbit heart. 965 35

It is well established that prolactin (PRL) sustains, while prostaglandin F(2 alpha) (PGF(2 alpha)) curtails, progesterone production by the rat corpus luteum (CL). We have previously shown that the actions of both molecules converge on the 20 alpha-HSD gene and control its expression in a dramatically opposed manner. In this investigation, we have found twelve more genes that are inversely regulated by PRL and PGF(2 alpha). In addition to 20 alpha-HSD, PGF(2 alpha) stimulated and PRL inhibited PGF(2 alpha)-receptor, phospholipase C delta(1) and TGF beta(1) expression. In contrast PRL stimulated and PGF(2 alpha) inhibited the LH receptor, 11 beta-HSD2, sterol carrier protein 2, mitochondrial glutathione S-transferase (GST), GST mu(2), inhibitory DNA-binding proteins 1, 2, and 3, and calcium binding protein 2. We have also identified new target genes for PRL and PGF(2 alpha). PGF(2 alpha) stimulated the expression of genes involved in cell signaling such as cell adhesion kinase-beta, ERK3, FRA2, IL-2 receptor, and 14-3-3 proteins. PGF(2 alpha) also up-regulated the expression of the sodium channel beta(1), Na/K ATPase, annexin IV, GST7pi, and P450 reductase. In contrast PGF(2 alpha) inhibited the expression of two genes involved in cell cycle: cyclin D2 and retinoblastoma related protein (Rb2/p130). It also inhibited genes involved in estradiol (P-450(AROM)) and cholesterol biosynthesis (HMG-CoA synthase), as well as genes involved in tissue remodeling: VEGF and TIMP3. PRL had a profound inhibitory effect on the expression of genes encoding the ADP-ribosylation factor 3, annexin V and c-jun, yet increased the expression of P450scc, 3beta-HSD, and SR-B1 (HDL-receptor), all genes involved in steroidogenesis. PRL also stimulated the expression of beta(2)-microglobulin, TIMP2, cytochrome c oxidase IV, cathepsin H and L, and copper-zinc superoxide dismutase as well as elongation factor SIII, heat shock protein-60 and mitochondrial ATP synthase-D. In conclusion, this investigation has revealed a "yin-yang" relationship between PRL and PGF(2 alpha) in regulating certain critical genes in the rodent CL, and has demonstrated novel regulation by these factors of other important genes involved in luteal function.
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PMID:Opposite effect of prolactin and prostaglandin F(2 alpha) on the expression of luteal genes as revealed by rat cDNA expression array. 1151 96

Rapamycin inhibits the FK506-binding protein 12 (FKBP12)/mammalian target of rapamycin (mTOR) complex and causes cell cycle arrest in G1. The precise mechanism of growth inhibition by rapamycin is only partly understood. Rapamycin led to growth inhibition in the human prostate cancer cell lines LNCaP and PC3 cells after 72 h, ID50: 93 and 50 nM, respectively. Filter cDNA array analysis showed down-regulation by more than 0.75x by rapamycin in PC3 cells and LNCaP cells of the following genes: follistatin, eukaryotic initiation factor-4E (eIF4E), glucose-6-phosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH)-A, ATP synthase, heat shock protein (HSP)-1. Upregulation by more than 1.5x was found for: bone morphogenetic protein (BMP)-4, FKBP12, carcinoma embryonic antigen (CEA) precursor, eukaryotic initiation factor (eIF)-3 p36 subunit, latent transforming growth factor (TGF) beta binding protein (LTBP)1. Rapamycin induced BMP4 and reduced follistatin expression in PC3 cells. This resulted in a dose-dependent nuclear expression of Smad4 and activated the SBE4 Smad-reporter, indicating activation of TGFbeta/BMP signaling. Combining rapamycin with PI3K inhibition (LY294002) increased growth inhibition. These findings illustrate that Smad signaling plays a role in the anticancer effects of rapamycin and show that combination with PI3K inhibition improves growth inhibition.
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PMID:Rapamycin induces Smad activity in prostate cancer cell lines. 1259 18

The causative agent of Whipple's disease, Tropheryma whipplei, is a slow-growing bacterium that remains poorly-understood. Genetic characterization of this organism has relied heavily upon rRNA sequence analysis. Pending completion of a complete genome sequencing effort, we have characterized several conserved non-rRNA genes from T. whipplei directly from infected tissue using broad-range PCR and a genome-walking strategy. Our goals were to evaluate its phylogenetic relationships, and to find ways to expand the strain typing scheme, based on rDNA sequence comparisons. The genes coding for the ATP synthase beta subunit (atpD), elongation factor Tu (tuf), heat shock protein GroEL (groEL), beta subunit of DNA-dependent RNA polymerase (rpoB), and RNase P RNA (rnpB) were analyzed, as well as the regions upstream and downstream of the rRNA operon. Phylogenetic analyses with all non-rRNA marker molecules consistently placed T. whipplei within the class, Actinobacteria. The arrangement of genes in the atpD and rpoB chromosomal regions was also consistent with other actinomycete genomes. Tandem sequence repeats were found upstream and downstream of the rRNA operon, and downstream of the groEL gene. These chromosomal sites and the 16S-23S rRNA intergenic spacer regions were examined in the specimens of 11 patients, and a unique combination of tandem repeat numbers and spacer polymorphisms was found in each patient. These data provide the basis for a more discriminatory typing method for T. whipplei.
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PMID:Analysis of conserved non-rRNA genes of Tropheryma whipplei. 1274 4

Oral tongue carcinoma is an aggressive tumor that particularly affects chronic smokers, drinkers and betel squid chewers. Patients often present symptoms at a late stage, and there is a high recurrence rate after treatment. In this article, we report the first proteomic analysis of oral tongue carcinoma to globally search for tumor related proteins. Apart from helping us to understand the molecular pathogenesis of the carcinoma, these proteins may also have potential clinical applications as biomarkers, enabling the tumor to be identified at an early stage in high risk individuals, treatment response to be predicted, and residual or recurrent carcinoma to be detected sooner after treatment. The protein expression profiles of ten oral tongue squamous cell carcinomas and their matched normal mucosal resection margins were examined by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectroscopy. A number of tumor-associated proteins including heat shock protein (HSP)60, HSP27, alpha B-crystalline, ATP synthase beta, calgranulin B, myosin, tropomyosin and galectin 1 were consistently found to be significantly altered in their expression levels in tongue carcinoma tissues, compared with their paired normal mucosae. The expression profile portrays a global protein alteration that appears specific to oral tongue cancer. The potential of utilizing these tumor related proteins for screening cancer and monitoring recurrence warrants further investigation.
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PMID:Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics. 1473 Jun 89

Acetyl-L-carnitine (ALC) is a molecule widely present in the central nervous system (CNS) formed by the reversible acetylation of carnitine. It acts by stimulating energy metabolism. Reported neurobiological effects of this substance include modulation of brain energy and phospholipid metabolism; cellular macromolecules (including neurotrophic factors and neurohormones); synaptic transmission of multiple neurotransmitters. ALC is of considerable interest for its clinical application in Alzheimer's disease and in the treatment of painful neuropathies. There are experimental data that it affects attention and antagonizes deterioration of ability to learn, improving long-term memory. Moreover, ALC influences nonassociative learning of sensitization type in Hirudo medicinalis. These findings are suggesting that ALC might exert its effects by means of new protein synthesis. ALC or saline solution was injected intraperitoneally each day for 21 days in rats. Poly(A)+ RNAs were isolated from control and treated rat brain. Suppression subtractive hybridisation (SSH) method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatments. The technique generates an equalized representation of differentially expressed genes irrespective of their relative abundance, and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated or switched off/on after ALC treatment. We identified two modulated genes, the isoform gamma of 14-3-3 protein and a precursor of ATP synthase lipid-binding protein, and one gene switched on by the treatment, the heat shock protein hsp72.
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PMID:Identification of differentially expressed genes induced in the rat brain by acetyl-L-carnitine as evidenced by suppression subtractive hybridisation. 1554 29

To probe the mitochondrial involvement in Mn intoxicity, aliquots of brain mitochondria samples from control and treated (30 mg/kg manganese chloride, ip) male Sprague-Dawley rats were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and searched for protein abundance changes induced by Mn exposure. The electrophoretic separation resolved over 300 distinct spots as visualized by colloidal Coomassie blue (CCB), of which three spots were induced and three spots were inhibited after Mn exposure in all the five brain mitochondria preparations. Analysis by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) indicated that these spots are calcium-transporting ATPase type 2C (ATP-dependent Ca(2+) pump PMR1); 60-kDa heat shock protein; Mitochondrial transmembrane GTPase FZO1B; ATP-binding cassette, sub-family b; Long-chain-fatty-acid-CoA ligase; ATP Synthase Beta Chain; and Succinate dehydrogenase flavoprotein subunit. The changes of the mitochondrial ATP synthase beta-subunit and Succinate dehydrogenase flavoprotein subunit indicate an effected level of mitochondrial ATP content and/or ATP-producing capacity. This result provides suggestion that respiratory chain complexes were implicated in the mitochondrial dysfunction induced by Mn intoxicity. And the changes of 60-kDa heat shock protein and ATP-dependent Ca(2+) pump PMR1 expression indicate that the Ca homeostasis and stress effect were involved in Mn intoxicity.
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PMID:Changes in the brain mitochondrial proteome of male Sprague-Dawley rats treated with manganese chloride. 1558 72


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