Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TGF-beta 1 has been examined in the heart during myocardial infarction caused by ligation of the left coronary artery. Infarcted and uninfarcted myocardium have been compared by immunohistochemical staining of TGF-beta 1 and by Northern blot analysis of mRNA. Normal ventricular myocytes are strongly stained by an antibody to TGF-beta 1. Progressive loss of staining of these myocytes begins within 1 hr after coronary ligation. However, by 24-48 hr after ligation, intense staining of myocytes at the margin of infarcted areas is seen. Northern blots of infarcted myocardium 48 hr after ligation show a 3- to 4-fold increase in the principal 2.4 kb TGF-beta 1 mRNA; there is also a marked increase in a minor 1.9 kb transcript. In the same tissue samples, there is a 2-fold decrease in the mRNA for the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase. The results indicate a significant role for TGF-beta in the response of the heart to injury.
 ...
PMID:Transforming growth factor beta-1 in acute myocardial infarction in rats. 307 66

The vascular endothelium is an important mediator of vascular tone, angiogenesis, inflammatory-immune reactions, vascular permeability, and hemostasis. Thus, it plays an important role in the pathogenesis of numerous critical care processes, including septic shock, myocardial infarction, the adult respiratory distress syndrome, and acute tubular necrosis. Endothelial functions may be altered by changes in the local cellular environment, particularly changes in PO2. The ability of endothelial cells (EC) to not only sense, but also to adapt to, acute and chronic changes in PO2 is critical to maintaining endothelial metabolic functions and, in turn, to maintaining homeostasis, particularly in the critical care setting. Recent studies have shown that the EC is one of the more hypoxia-tolerant mammalian cell types; however, the mechanisms by which ECs respond and adapt to hypoxia are unknown. Our laboratory has shown that cultured ECs exposed to hypoxia upregulate a set of stress proteins, termed hypoxia-associated proteins (HAPs), that are distinct from the classically described stress proteins induced by heat shock (heat-shock proteins) or glucose deprivation (glucose-regulated proteins). We have recently identified one of these proteins as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Further studies have shown that GAPDH expression is regulated by hypoxia, primarily at the transcriptional level. Subcellular fractionation of hypoxic EC has shown that GAPDH is upregulated in the cytoplasmic fraction as would be expected with a glycolytic enzyme; however, a protein corresponding to GAPDH is also upregulated in the nuclear fraction. This suggests that the upregulation of GAPDH in EC during hypoxia is related to the potential nonglycolytic functions of this enzyme. Furthermore, the upregulation of GAPDH and the other HAPs (that have yet to be identified) may be related to the relative hypoxia tolerance of EC.
 ...
PMID:Hypoxia-associated proteins. 758 62

The mammalian heart is normally well oxygenated and anaerobic glycolysis is extremely rare except for the production of extra ATP during extreme exercise like a marathon race. Anaerobic glycolysis plays a role when there is a serious impairment in coronary blood flow such as during heart attack and open heart surgery. The control of glycolysis in ischemic myocardial tissue appears to be extremely complex. During aerobic glycolysis, phosphofructokinase is the most important regulatory enzyme that controls the energy requirements of the cell. Under anaerobic conditions, however, glyceraldehyde-3-phosphate dehydrogenase becomes the key enzyme because it responds promptly to any changes in the essential supply of co-factors for oxidation. The conversion of pyruvate to acetyl CoA (aerobic metabolism) involves a series of chain reactions primarily catalyzed by pyruvate dehydrogenase complex which is situated at the cross roads between both aerobic and anaerobic glycolysis. It is important to remember that substrate utilization is carefully controlled by substrate availability. During aerobic metabolism, control mechanisms using fatty acids, lactate and glucose as energy substrates regulate the rate of ATP production according to energy demand. This precise mechanism is upset during ischemia and post-ischemic reperfusion for reasons discussed in this review. The demand for ATP can no longer be met by its supply because of severely reduced anaerobic glycolysis and significantly inhibited beta-oxidation of fatty acids. The impairment of bioenergetics is discussed in the context of several diseases such as cardiomyopathy, heart failure, diabetes, arrhythmias, cardiac surgery, heart-lung transplantation, and also in aging and oxidative stress. The regulation of energy metabolism in preconditioned heart is also discussed. Finally, methods used to preserve energy in ischemic myocardium are summarized and quantitation of the high-energy phosphates is discussed. This review challenges scientists to discover drugs which will stimulate energy supply during myocardial ischemia.
 ...
PMID:Bioenergetics, ischemic contracture and reperfusion injury. 880 94

Endothelin-converting enzyme-1 (ECE-1) plays a substantial role in activation of the endothelin (ET) system by cleaving the precursor, big ET-1, to the active peptide ET-1. The aim of this study was to investigate whether ECE-1 mRNA expression is modified in human cardiovascular disease. ECE-1 expression was related to echocardiographic data, drug treatment, age, sex, and NYHA heart failure classification. A quantitative PCR assay (qPCR) was established to measure ECE-1 mRNA in these samples. The ECE-1 measurements were normalized over a simultaneously performed GAPDH qPCR. The results indicate a higher ECE-1 expression level in atrial tissue samples of patients who have experienced a myocardial infarction compared with those who did not (ECE-1/GAPDH: 5.81 +/- 0.76 fg/ng; n = 21 vs. 3.20 +/- 0.51 fg/ng; n = 22; p = 0.007). The transverse diameter of the left atrium over 37 mm was associated with a lower ECE-1 expression (ECE-1/GAPDH: 3.11 +/- 0.69 fg/ng; n = 18 vs. 5.12 +/- 0.65 fg/ng; n = 25; p = 0.044). In assessing the drug treatment, decreased ECE-1 expression could be observed in patients who received a beta-blocker (ECE-1/GAPDH: 3.90 +/- 58 fg/ng; n = 31 vs. 5.81 +/- 0.76 fg/ng; n = 12; p = 0.077). These data suggest an involvement of the ET system is cardiovascular disease that may be clinically important.
 ...
PMID:Endothelin-converting enzyme-1 mRNA expression in human cardiovascular disease. 959 98

Creatine kinase (CK) plays a crucial role in cardiac energy transduction. During chronic cardiac stress conditions leading to hypertrophy and/or heart failure, the profile of CK isoenzyme activities changes towards a fetal pattern with increases of BB- and MB-CK and decreases of MM-CK and mito-CK. Changes of myocardial CK gene expression are only indirectly reflected by measurements of CK activities. The purpose of this work was, therefore, to determine myocardial expression of B-, M- and sarcomeric mito-CK genes in an animal model of heart failure where hemodynamic alterations and CK system changes are well defined, that is, in the rat heart post-myocardial infarction. Intact residual left ventricular myocardium was harvested 2 months following infarction (MI; n = 7) or sham operation (sham; n = 6) after in vivo left-ventricular end-diastolic pressure (LVEDP) was recorded. Total CK activity was measured spectrophotometrically, CK isoenzyme distribution with agarose gel electrophoresis. Steady state mRNA levels coding for B-, M- and mito-CK genes were measured with quantitative PCR and were normalized for GAPDH expression. Total CK activity tended to be reduced in MI (5.51 +/- 0.62 IU/mg protein) compared to sham (6.77 +/- 0.24; P = 0.55). CK isoenzyme distribution showed an increase of fetal BB- + MB-CK (MI 22.0 +/- 3.1%, sham 15.1 +/- 1.0%; P < 0.05), no change of MM-CK and a decrease of mito-CK (27.0 +/- 1.5% sham, 20.8 +/- 2.0% MI: P < 0.05). Relative B-CK mRNA levels increased (sham 0.46 +/- 0.06, MI 1.03 +/- 0.09; P < 0.05) and M-CK mRNA levels decreased (sham 1.06 +/- 0.08. MI 0.66 +/- 0.09; P < 0.05) significantly post-MI. The increase of B-CK mRNA (r = 0.72; P = 0.009) and the decrease of M-CK mRNA (r = 0.76; P = 0.003) correlated significantly with in vivo LVEDP. Mito-CK mRNA levels remained unchanged after MI (sham 0.94 +/- 0.16, MI 0.98 +/- 0.09). Intact residual left-ventricular myocardium post-MI is characterized by increased B-CK-mRNA and reduced M-CK-mRNA expression.
 ...
PMID:Changes of creatine kinase gene expression in rat heart post-myocardial infarction. 960 29

Endothelin-1 converting-enzyme (ECE-1) cleaves the precursor, big-endothelin-1, to the active peptide endothelin-1. The aim of this study was to investigate whether ECE-1 mRNA expression is modified in human cardiovascular disease. Tissue samples from the left human atrium were analyzed for ECE-1 expression and related to different clinical parameters. A quantitative PCR assay (qPCR) with competitive and non-competitive standards was established. The ECE-1 measurements were normalized by a GAPDH qPCR. Patients who suffered from a myocardial infarction had elevated ECE-1 levels when compared to controls (5.81+/-0.76 vs. 3.20+/-0.51 fg ECE-1, ng GAPDH, p<0.05). Drug treatment with the beta-blocker metoprolol was associated with a decreased ECE-1 expression level (3.90+/-0.58 vs. 5.81+/-0.76 fg ECE-1, ng GAPDH, p<0.1). We conclude that the expression of ECE-1 is altered in the atrial tissue depending on the physiological status of the heart. This suggests a differential role of ECE-1 in cardiovascular diseases.
 ...
PMID:Endothelin converting-enzyme-1 mRNA expression in human cardiovascular disease. 960 4

The aim of this study was to analyze sequential change of angiotensinogen (Ao) mRNA expression in rat liver and noninfarcted myocardium after myocardial infarction (MI). Female sprague-Dawley rats were subjected either to left coronary artery occlusion or sham operation. Three weeks after MI, coronary artery ligation resulted in comparable infarct sizes. A hypokinetic thin anterior wall and remarkable dilatation of the left ventricle, as well as decreased contractility (left ventricular end-systolic dimension = 6.0+/-0.4, 3.3+/-0.2, LV end-diastolic dimension = 7.9+/-0.3, 5.9+/-0.2 mm, and fractional shortening = 25.3+/-3.1%, 45.1+/-3.3%) were shown in the MI and sham group, respectively, by echocardiography (P < 0.01). Experimental MI caused a significant fall in systolic blood pressure (MI 90+/-5.0, vs sham 130+/-7.5 mmHg; P< 0.01) and significantly higher left ventricular end-diastolic pressure (MI 21+/-1.5, vs sham 11+/-1.0 mmHg: P < 0.01). At 4, 18, and 24h after MI, liver Ao mRNA levels, as shown by Northern blot analysis, had increased by up to four times (Ao/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) = 1.4+/-0.1 and 6.0+/-0.2 at baseline and 4h after MI, respectively (P < 0.01). After sham surgery, however, the corresponding increase was slight (maximal 1.5-fold). Three days after MI, liver mRNA had returned to the baseline level. In contrast, ATG mRNA expression in noninfarcted myocardium, as shown by reverse transcription-polymerase chain reaction and Southern blotting, decreased transiently during the acute phase. It returned to its baseline level within 3 days, and then increased further (Ao/ GAPDH = 2.9+/-0.6, 0.3+/-0.1, 3.2+/-0.8, and 3.7+/-0.8 at baseline, 24h, 3 days, and 3 weeks after MI, respectively). In conclusion, it can be stated that after MI, the Ao gene contributes, acutely in the liver and chronically in the myocardium, to the maintenance of hemodynamic homeostasis during the acute phase and ventricular remodeling during the chronic phase.
 ...
PMID:Reciprocal change in angiotensinogen mRNA expression in rat myocardium and liver after myocardial infarction. 992 59

An injury to the heart due to myocardial infarction (MI) may progress to heart failure. Among factors, whose interactions promote remodeling of ischemic myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor (VEGF) was found. However, little is known about the temporal and spatial relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for experimental myocardial infarction. The procedure was performed by anterolateral thoracotomy and snearing LAD with the metal clip. The hemodynamic measurements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188 along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No expression of examined genes was detected in the myocardium of control rats. The expression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These findings confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in the remodeling of the myocardium and development of heart failure after experimental myocardial infarction.
 ...
PMID:Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats. 1132 12

The sequelae of chronic hyperglycemia in diabetes of all phenotypes are divided into microvascular and macrovascular complications. Microvascular disease causes blindness, renal failure, and neuropathy, and diabetes-accelerated macrovascular disease causes excessive risk for myocardial infarction, stroke, and lower limb amputation. The link between chronic hyperglycemia and vascular damage has been established by four independent biochemical abnormalities: increased polyol pathway flux, increased formation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), and increased hexosamine pathway flux. These seemingly unrelated pathways have an underlying common denominator: overproduction of superoxide by the mitochondrial electron transport chain. Mitochondrial reactive oxygen species (ROS) partially inhibit the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, which diverts increased substrate flux from glycolysis to pathways of glucose overutilization. Preliminary experimental evidence in vivo suggests that this new paradigm provides a novel basis for research and drug development.
 ...
PMID:Pathophysiological mechanisms of diabetic angiopathy. 1262 64

1. Myocardial infarction (MI) poses a significant risk for sudden cardiac death. The effectiveness of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockade in attenuating unfavourable post-MI outcomes indicates an important role for angiotensin (Ang) II signalling in the post-MI remodelling process. 2. AT1 and AT2 receptor expression is known to be altered during the early postinjury period and at the later failure stage in the infarcted heart. The aim of the present investigation was to characterize AngII receptor expression shifts in the intermediate, adaptive phases of post-MI hypertrophic remodelling. 3. The present study investigated relative cardiac AT1 and AT2 receptor expression levels using semiquantitative reverse transcription-polymerase chain reaction (GAPDH normalized) in rats at 4 and 20 weeks after ligation of the left anterior descending coronary artery. 4. Heart weight and normalized heart weight were significantly higher in the MI group than in the sham group 4 weeks post-MI, with significant hypertrophy of the left ventricle, left atrium and right ventricle in MI rats. At 20 weeks post-MI, left ventricular hypertrophy remained significant, whereas the mass of the other cardiac tissues was not different to that of sham controls. 5. AT2 receptor expression was markedly reduced in both the non-infarct and infarcted areas of the left ventricular wall in the MI group compared with the sham-operated group 4 weeks after surgery. Expression levels were reduced to 8 and 13% of sham values in the viable and scar tissue regions, respectively. By 20 weeks post-MI, there was no evidence of AT2 receptor expression suppression in the left ventricle. No significant relative changes in AT1 receptor mRNA levels were observed at either 4 or 20 weeks post-MI. 6. The present study demonstrates, for the first time, a selective downregulation of left ventricular AT2 receptor expression in the intermediate phase of post-MI ventricular remodelling in the rat. This downregulation may provide an enhanced AT1 receptor-mediated compensatory progrowth signal in the early adaptive post-MI growth phase. A more detailed understanding of the time-course of differential AT1 and AT2 receptor expression regulation post-MI may potentially identify an optimal window for targeted pharmacological intervention in the treatment of MI.
 ...
PMID:Transitory reduction in angiotensin AT2 receptor expression levels in postinfarct remodelling in rat myocardium. 1529 43


1 2 Next >>