Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon exchange in the Krebs cycle may result in underestimation of substrate oxidation measured with 13C-labeled substrates, since carbon labeled in position 2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via gluconeogenesis) and glutamine. Five healthy volunteers were therefore infused with [1-13C] and [2-13C] acetate at a rate of 0.5 micromol x kg(-1) x min(-1) for 165 minutes on two different occasions in randomized order. Whole body acetate turnover did not differ between the two tracers: 7.9+/-0.3 and 7.5+/-0.6 micromol x kg(-1) x min(-1) (nonsignificant [NS]) for [1-13C] and [2-13C] acetate, respectively. Isotopic 13C enrichment was higher in expired CO2 (0.177+/-0.021 v 0.089+/-0.009 atom percent excess [APE], P < .01) and lower in glucose (0.074+/-0.017 v0.291+/-0.061 mole percent excess [MPE], P < .01) for [1-13C] acetate compared with [2-13C] acetate, respectively, at the end of the infusions. Glutamine isotopic enrichment was slightly but not significantly higher when infusing [1-13C] acetate versus [2-13C] acetate (0.348+/-0.038 v0.495+/-0.069 MPE, NS, respectively). At the end of the experiment, the recovery of 13CO2 from [1-13C] acetate was 44.8%+/-2.7%, and from [2-13C] acetate, 22.6%+/-1.3%. A significant correlation was observed between the differences in 13C enrichment of CO2 for the two tracers and glucose (deltaCO2=0.424 x deltaglucose + 0.001, R2=.9856, P=.0007) or glutamine (deltaCO2=0.621 x deltaglutamine + 0.004, R2=.9573, P=.0038) during the infusion. These results suggest that (1) although gluconeogenesis appears to be more responsible than glutamine for the differential recovery of [2-13C] versus [1-13C] acetate, other secondary pathways are probably also implicated; and (2) different recovery correction factors should be applied when measuring substrate oxidation with a stable isotope tracer depending on the expected position of 13C in acetyl-CoA.
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PMID:Role of glucose and glutamine synthesis in the differential recovery of 13CO2 from infused [2-13C] versus [1-13C] acetate. 959 45

Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. In different melanoma cell lines, we found that both nucleus and cytoplasm exhibited higher levels of Ref-1 compared with normal melanocytes. Similar increases of Ref-1 expression, detected by immunohistofluorescence, were also evident in nevi and malignant melanoma biopsies compared with normal skin, which were predominantly localized in the nucleus. Using recombinant adenovirus Adref-1, encoding full-length Ref-1, we transiently overexpressed APE/Ref-1 in human melanocytes, which protected these cells from UVB-induced apoptosis and increased foci formation in culture. Ref-1 overexpression also protected melanoma cells from cisplatin- or H2O2-induced apoptosis, whereas increased apoptosis was observed with Ref-1 antisense construct infection. These observations suggested that intracellular Ref-1 levels played an important role in sensitization of melanoma cells to apoptosis. Electrophoretic mobility shift assay results showed that in both cultured primary and metastatic melanomas DNA-binding activities of activator protein-1 and nuclear factor-kappaB were significantly diminished or shifted when anti-APE/Ref-1 antibody was added to deplete APE/Ref-1 from the binding complexes. Induced nuclear factor-kappaB transcriptional activities were also evident after Ref-1 overexpression. Furthermore, using three-dimensional molecular structure modeling and virtual screening, we found that resveratrol, a natural compound found in fruits and vegetables, docks into a druggable pocket of Ref-1 protein. In vitro studies revealed that resveratrol inhibited, in a dose-dependent manner, Ref-1-activated activator protein-1 DNA-binding activities as well as Ref-1 endonuclease activities and rendered melanoma cells more sensitive to dacarbazine treatment.
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PMID:Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor. 1637 7