Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the tumor host response to excessive doses of an anabolic steroid (nandrolone propionate, 2.5 mg 20 g intraperitoneally every second day for 11 days) with respect to body composition and tumor cell kinetics in MCG 101 sarcoma-bearing mice (C57BL/6J) with progressive cachexia. Although survival and food intake were not affected, a significant weight gain was observed that was essentially attributed to water retention. Net protein content was increased only to a minor extent (15%), of which only the liver accounted for a significant part of the body compartments. Hepatic protein accumulation was obviously caused by decreased protein degradation, since hepatic RNA content was unchanged. After anabolic steroid administration, reduced histochemical staining of succinate dehydrogenase was observed in skeletal muscles rich in oxidative type 1 fibers, but it was not different from that of tumor-bearing control animals, which was also confirmed by measurements of citrate synthase and cytochrome c oxidase activities in skeletal muscle and liver tissue. The anabolic steroid had no significant effect on tumor growth in terms of weight progression, energy state, polyamine synthesis rate, cell division rate, and cell cycle cytocompartments. We conclude that anabolic steroid supplementation is not therapeutically beneficial in counteracting progressive weight loss in experimental cancer.
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PMID:Effects of nandrolone propionate on experimental tumor growth and cancer cachexia. 772 66

The elevated rate of oxygen consumption and high amount of polyunsaturated fatty acids make the central nervous system vulnerable to oxidative stress. The effect of Walker-256 tumor growth on oxi-reduction indexes in the hypothalamus (HT), cortex (CT), hippocampus (HC) and cerebellum (CB) of male Wistar rats was investigated. The presence of the tumor caused an increase in thiobarbituric acid reactant substances (TBARs) in the HT, CB and HC. Due to tumor growth, the activity of glucose-6-phosphate dehydrogenase increased in the HT and CB, whereas citrate synthase activity was reduced in the HT, CT and CB. Therefore, the potential for generation of reducing power is increased in the cytosol and decreased in the mitochondria of various brain regions of Walker-256 tumor-bearing rats. These changes occurred concomitantly with an unbalance in the brain enzymatic antioxidant system. The tumor decreased the activities of catalase in the HT and CB and of glutathione peroxidase in the HT, CB and HC, and raised the CuZn-superoxide dismutase activity in the HT, CB and HC. These combined findings indicate that Walker-256 tumor growth causes oxidative stress in the brain.
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PMID:Walker-256 tumor growth causes oxidative stress in rat brain. 1129 28

Angiogenesis is a tightly regulated process, both during development and adult life. Animal models with mutations in the genes coding for placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, or the tyrosine kinase domain of the PlGF receptor (Flt-1) have revealed differences between normal physiological angiogenesis and pathological angiogenesis associated with conditions such as tumor growth, arthritis and atherosclerosis. In the present paper, we investigated the potential role of PlGF in regulating physiological angiogenesis by analyzing vascular changes in heart and skeletal muscles of wild-type and Plgf-/- mice following prolonged and sustained physical training. Sedentary Plgf-/- mice showed a reduced capillary density in both heart and skeletal muscles as compared to wild-type mice (P < 0.05). However, after a 6-week training period, heart/body weight ratio, citrate synthase activity, vessel density and capillary/myocyte ratio were significantly increased in both wild-type and Plgf-/- mice (all P < 0.05). At the same time intercapillary distance was significantly reduced. Finally, acute exercise was not associated with any change in PlGF protein level in the skeletal muscle. Our results demonstrate that PlGF is not necessary for exercise-training-induced angiogenesis. We thus suggest that the role of PlGF is confined to the selective regulation of angiogenesis only under pathological conditions.
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PMID:Placenta growth factor is not required for exercise-induced angiogenesis. 1560 82

Malignant tumors often display an aberrant energy metabolism that relies primarily on glycolysis to produce adenosine triphosphate (ATP) the so-called Warburg effect or aerobic glycolysis. Thus, the elucidation of this energetic alteration in malignant tumors is important in the search for more effective therapeutics against malignant cancers, the most deadly human disease. To investigate whether attenuated glycolytic activity modulates tumor progression, the effects of silencing the first and rate-limiting glycolytic enzyme hexokinase (HK) isozymes HK1 and HK2 were examined. There was an inverse correlation between the expression of HK1 and HK2 in human cancer cells. In cervical carcinoma cells, the HK1 but not HK2 knockdown induced a phenotypic change characteristic of epithelial-mesenchymal transition, which accelerated tumor growth and metastasis both in vitro and in vivo analyses. Notably, the silencing of HK1 disrupted aerobic respiration and increased glycolysis, but it had no effect on ATP generation. These metabolic changes were associated with higher HK2 and lactate dehydrogenase 1 expression but a lower citrate synthase level. Particularly, the HK1 knockdown induced aberrant energy metabolism that was almost recapitulated by HK2 overexpression. Moreover, the HK1-silenced cells showed strong glucose-dependent growth and 2-deoxyglucose (2-DG) induced cell proliferation inhibition. These results clearly indicate that the silencing of HK1, but not HK2, alters energy metabolism and induces an EMT phenotype, which enhances tumor malignancy, but increases the susceptibility of cancer cells to 2-DG inhibition. In addition, this work also suggests that the glycolytic inhibitors should be used only to treat cancers with elevated glycolytic activity.
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PMID:The decrease of glycolytic enzyme hexokinase 1 accelerates tumor malignancy via deregulating energy metabolism but sensitizes cancer cells to 2-deoxyglucose inhibition. 2972 Nov 75