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

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The union of calcium cations with carbonate anions to form calcium carbonate (CaCO3) is a fundamentally important physiological process of many marine invertebrates, in particular the corals. In an effort to understand the sources and processes of carbon uptake and subsequent deposition as calcium carbonate, a series of studies of the incorporation of 14C-labeled compounds into spicules was undertaken using the soft coral Leptogorgia virgulata. It has been surmised for some time that dissolved inorganic carbon in sea water is used in the biomineralization process. Furthermore, it was suspected that metabolically generated CO2 is also available for calcification. As a means of testing these possible sources of carbon in spicule calcification, key enzymes or transport systems in each pathway were inhibited. First, the enzyme carbonic anhydrase was specifically inhibited using acetazolamide. Second, the active transport of bicarbonate was inhibited using DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid). Third, CO2 generation resulting from glycolysis and the citric acid cycle was arrested using iodoacetic acid, which interferes specifically with the enzyme glyceraldehyde-3-phosphate dehydrogenase. The results indicate that dissolved CO2 is the largest source of carbon used in the formation of calcitic sclerites, followed by HCO3- from dissolved inorganic carbon. In L. virgulata, the dissolved inorganic carbon is responsible for approximately 67% of the carbon in the sclerites. The other 33% comes from CO2 generated by glycolysis. Two important conclusions can be drawn from this work. First, carbon for spiculogenesis comes not only from dissolved inorganic carbon in the environment but also from metabolically produced carbon dioxide. While the latter has been theorized, it has never before been demonstrated in octocorals. Second, regardless of the carbon source, the enzyme carbonic anhydrase plays a pivotal role in the physiology of spicule formation in Leptogorgia virgulata.
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PMID:A physiological evaluation of carbon sources for calcification in the octocoral Leptogorgia virgulata (Lamarck). 935 72

Our objective in experiments reported here was to identify myofilament proteins of rat hearts either lost or degraded by cardiac ischemia (15- or 60-minute duration) with and without 45 minutes of reperfusion. We correlated these changes with alterations in myofilament sensitivity to Ca2+ and maximum force generation. Protein degradation and loss were assessed by high-performance liquid chromatography, SDS-PAGE, Western blotting analysis, and amino acid sequencing. Compared with nonischemic control hearts, bundles of skinned fibers from hearts subjected to ischemia alone demonstrated a decrease in maximum force generation and an increase in sensitivity to Ca2+. These changes in function were increased with the duration of the ischemia and with reperfusion. With increasing duration of ischemia, there was an increased loss and degradation of myofibrillar alpha-actinin and troponin I (TnI) at its C-terminus. Alpha-actinin and TnI were most susceptible to ischemia, but with 60 minutes of ischemia/reperfusion, there was also degradation of myosin light chain-1 (MLC1) involving a clip of residues 1 to 19. The MLC1 degradation product was detected in the reperfusion effluent (along with troponin T, tropomyosin, and alpha-actinin) but not in the tissue with 60 minutes of ischemia with no reperfusion. Moreover, with ischemia the following proteins became associated with the myofibrils: GAPDH and proteins of the mitochondrial ATP synthase complex. Our results provide new evidence regarding the mechanism by which ischemia/reperfusion causes myocardial injury and support the hypothesis that an important element in the injury is altered activity and structure of the myofilaments.
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PMID:Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa-force relation. 946 97

Cerebral ischemia is known to modify the expression of genetic information in the brain. To complement this knowledge, in the present study we have estimated the expression of calcium- and phospholipid-dependent (classical) protein kinase C (c PKC) isoform mRNAs (alpha, beta1 and gamma) at different time following ischemia. Forebrain cerebral ischemia was performed on Mongolian gerbils by 5 minutes bilateral occlusion of common carotid arteries. At the pointed time the cytoplasmic RNA was extracted from hippocampus and the expression of PKC mRNA quantified by RT PCR technique using GAPDH expression as an internal standard. Results indicate that only one gamma isoform of cPKC mRNA expression becomes significantly modified in postischemic hippocampus. A transient increase up to 145% of control within the first 3 h was followed by its decline to 60-65% at a longer recirculation period. This lowered levels returned back to control at 72 h postischemic recovery. This result indicates that gamma PKC could be particularly sensitive to ischemic insult and would react in accordance with the other early signals determining ischemic outcome.
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PMID:Expression of Ca2+-dependent (classical) PKC mRNA isoforms after transient cerebral ischemia in gerbil hippocampus. 947 87

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is induced by hypoxia in endothelial cells (EC). To define the mechanisms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt, other transition metals, carbon monoxide (CO), deferoxamine, or cycloheximide in the presence or absence of hypoxia for 24 h, and GAPDH protein and mRNA levels were measured. GAPDH was induced in cells by the transition metals cobalt, nickel, and manganese and by deferoxamine, and GAPDH mRNA induction by hypoxia was blocked by cycloheximide. GAPDH induction by hypoxia, unlike that of other hypoxia-regulated genes, was not inhibited by CO or by 4,6-dioxoheptanoic acid, an inhibitor of heme synthesis. GAPDH induction was not altered by mediators of protein phosphorylation, a calcium channel blocker, a calcium ionophore, or alterations in redox state. GAPDH induction by hypoxia or transitional metals was partially blocked by sodium nitroprusside but was not altered by the inhibitor of nitric oxide synthase N omega-nitro-L-arginine. These findings suggest that GAPDH induction by hypoxia in EC occurs via mechanisms other than those involved in other hypoxia-responsive systems.
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PMID:Hypoxic regulation of endothelial glyceraldehyde-3-phosphate dehydrogenase. 948 23

The membrane fusion events observed during neutrophil degranulation are important aspects of the immunoregulatory system. In an attempt to understand the regulation of granule-plasma membrane fusion, we have begun characterizing human neutrophil cytosol for fusion activity, finding that 50% of the fusogenic activity could be attributed to members of the annexin family of proteins. The major non-annexin fusion activity (25% of the total cytosolic activity) was enriched by ion exchange chromatography after depletion of annexins by Ca2+-dependent phospholipid affinity chromatography. The fusion activity co-purified with a 10,14-kDa dimer identified as leukocyte L1 (which was non-fusogenic), along with an approximately 36-kDa protein. This protein was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by amino-terminal sequencing, and the fusion activity was verified using commercially available GAPDH. GAPDH may play an important role in degranulation because it is as potent as annexin I on a mass basis and may constitute up to 25% of the total cytosolic fusion activity of the neutrophil.
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PMID:Identification of glyceraldehyde-3-phosphate dehydrogenase as a Ca2+-dependent fusogen in human neutrophil cytosol. 950 May 20

The aim of the present study was to test the hypothesis that the decreased renal tubular reabsorption of calcium observed in estrogen deficiency is associated with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40) during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in untreated OVX animals than in all other groups (P < 0.01). Plasma PTH was higher in OVX+E40 than in OVX+E4 (P < 0.05). PTHrP mRNA expression in the kidney was unaffected by ovariectomy but was increased in OVX+E40 (0.984 +/- 0.452 for PTHrP/GAPDH mRNAs expression vs. 0.213 +/- 0.078 in sham, P < 0.01). PTH/PTHrP receptor mRNA expression and the cAMP response of renal membranes to PTH were unaffected by ovariectomy and estrogen substitution. In conclusion, renal PTHrP and PTH/PTHrP receptor mRNAs are not modified by ovariectomy. However, 17beta-estradiol increases renal expression of PTHrP mRNA without evident changes in its receptor expression and function. This may help to explain the pharmacological action of estrogen in the kidney, especially how it prevents the renal leak of calcium in postmenopausal women.
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PMID:Estrogen stimulates PTHrP but not PTH/PTHrP receptor gene expression in the kidney of ovariectomized rat. 963 10

Sarcoplasmic reticulum (SR) Ca2+-ATPase gene expression is reduced in the failing myocardium. However, the functional relevance of these changes to myocardial contractility is not yet established. We assessed myocardial contractile function by analyzing sarcomere motion of isolated myocytes and also quantified SR Ca2+ regulatory protein gene expression by Northern blot analysis in the same hearts obtained from 10 dogs with pacing-induced heart failure (HF; 240 beats/min, 4 wk) and 7 control dogs. Sarcomere-shortening velocity was depressed in HF myocytes, accompanied by the prolongation of intracellular Ca2+ concentration ([Ca2+]i) transient measured by indo 1 fluorescence ratio. SR Ca2+-ATPase mRNA levels (normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly depressed in HF, and calsequestrin mRNA was increased. For control and HF dogs, sarcomere-shortening velocity correlated positively with Ca2+-ATPase mRNA levels (r = 0.73, n = 17, P < 0.01) but not with calsequestrin mRNA. Ca2+-ATPase mRNA levels were correlated with 45Ca2+ uptake rate by SR, which was also reduced in HF. Moreover, the inhibition of SR Ca2+-ATPase with thapsigargin or cyclopiazonic acid reproduced in normal myocytes the abnormalities observed in HF myocytes, such as depressed contractility and the prolonged [Ca2+]i transient duration. A downregulation of Ca2+-ATPase gene expression and a resultant decrease in Ca2+ uptake by SR may be responsible for the contractile dysfunction and the alterations of [Ca2+]i transient in HF.
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PMID:Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure. 968 93

Transglutaminase is a calcium-dependent enzyme which catalyzes amine incorporation and cross-linking of proteins. To isolate the amine acceptor protein substrates of transglutaminase in mammalian livers, a biotin-labeled primary amine substrate of transglutaminase, 5-(biotinamido) pentylamine, was used for biotin labeling of proteins in the liver extracts by endogenous transglutaminase activity. The biotin-labeled proteins were isolated and recovered by biotin-avidin-affinity chromatography. The obtained proteins were separated by SDS-PAGE. Proteins with molecular masses of 15, 24, 35, 40, 44, 93, and 134 kDa were the main components of labeled proteins in mouse liver extract. In rat and guinea pig liver extracts, 32-, 38-, 40-, 44-, and 134-kDa proteins and28-, 40-, 44-, 55-, 60-, 91-, and 134-kDa proteins were the main components of labeled proteins, respectively.Using amino-terminal amino acid sequence analyses and sequence homology searches, the 38-kDa protein from rat liver was identified as a subunit of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), and the 28-kDa protein from guinea pig liver was identified as a subunit of glutathione S-transferase (class theta) (EC 2.5.1.18). Both the glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle and glutathione S-transferase (class pi) from human placenta also could be amine acceptors in the amine incorporation catalyzed by guinea pig liver transglutaminase. These results suggest that these enzymes can be modified posttranslationally by cellular transglutaminase.
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PMID:Identification of amine acceptor protein substrates of transglutaminase in liver extracts: use of 5-(biotinamido) pentylamine as a probe. 970 18

This study was devoted to the continued search for an explanation of the neurodegeneration found in a severely TPI deficient Hungarian patient whose brother with genomically completely identical TPI defect was completely free of neurological disorders. The changes found in the molecular species composition of the major PL subclasses and the decrease in PE plasmalogens explain the earlier round increase in membrane fluidity interfering thereby with the physiological function of membrane enzymes, receptors, signal transduction, protein-protein interactions and vesicle fusion. Plasmalogens have also the capacity to protect against oxidative stress, that is deemed to contribute to neurodegenerative processes. The presence of chronic oxidative stress was well reflected in the decreased levels of GSH and alpha-tocopherol in the affected brothers. Decrease in plasmalogens have been described recently in Zellweger's syndrome, in other peroxisomal neurodegenerative disorders, in demyelinating processes and in Alzheimer's disease. The brain in normal individuals is highly enriched in plasmalogens. The pathological decrease found in TPI deficient lymphocytes will presumably be more pronounced in excitatory tissues. The recently described role of expanding nucleotide triplets in the development of neurodegeneration is suggested to result through the selective binding via their polyglutamine repeats to GAPDH. The role of GAPDH in TPI deficiency may be of crucial help in the elucidation of the development of neurodegeneration, since the enzymatic defect of TPI can be partially bypassed by means of the HMP shunt which generates GAP via GAPDH without the participation of TPI. Considering the results found in TPI deficiency in comparison to the new literary findings in different neurodegenerative diseases the following pathomechanism may be proposed. The protein products of the defective genes due to their abnormal steric structure bind GAPDH in a different manner or in differing quantity than their normal counterparts. The PL composition and the resulting differences in the biophysical properties of the cell membranes have crucial impact on these protein-protein interactions and on the activity of enzymes and membrane transport functions. The plasmalogen decrease impairs the protection against oxidative stress with consecutive worsening of the neurodegenerative process. The final common pathway to neuronal death leads through destabilization of intracellular Ca2+ homeostasis via elevation of intracellular Ca2+ to apoptosis. The most important conclusion is that lipids are not an inert environment of membrane proteins. Unravelling of the pathogenesis of neurodegeneration needs more concerted investigation of the interactions between genetic changes with biophysical and biochemical cell membrane lipid alterations.
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PMID:[Glycolytic enzyme defects and neurodegeneration]. 987 6

There is growing evidence that alterations in calcium (Ca2+) homeostasis may play a role in processes of brain aging and neurodegeneration. There also is evidence that some of the altered Ca2+ homeostasis in hippocampal neurons may arise from an increased density of L-type voltage sensitive Ca2+ channels (L-VSCC). In the present studies, we tested the possibility that previously observed increases in functional L-VSCC with aging might be related to up-regulated gene/mRNA expression for Ca2+ channel subunits. A significant aging-related increase in mRNA content for the alpha1D subunit of the L-type VSCC was observed in hippocampus of aged F344 rats (25 months old) relative to young (4 months old) and middle-aged animals (13 months old), as assessed by both in situ hybridization analyses (densitometry and grain density) and ribonuclease protection assay (RPA). In RPA analyses, the alpha1C subunit mRNA also showed a significant increase in 25-month-old rats. No age changes were seen in mRNA for the beta1b subunit of VSCC or for GAPDH, a standard control. The clearest increases in alpha1D mRNA expression were observed in subfield CA1, with little or no change seen in dentate gyrus. Although these results alone do not demonstrate that mRNA/gene expression changes contribute directly to changes in functional Ca2+ channels, they clearly fulfill an important prediction of that hypothesis. Therefore, these studies may have important implications for the role of gene expression in aging-dependent alterations in brain Ca2+ homeostasis.
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PMID:Up-regulation of alpha1D Ca2+ channel subunit mRNA expression in the hippocampus of aged F344 rats. 1019 18


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