Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hydrogen peroxide (H2O2) on the purine metabolism of human endothelial cells were investigated. An incubation with 0.01 mM H2O2 over 60 min led to an increase in the intracellular adenosine-5-triphosphate (ATP) and creatine phosphate (CP) levels by 51.3% and 18.2%, respectively. A 60 min incubation with 0.1 mM H2O2 showed no effect. The uptake and salvage of 14C-adenine (14C-AD) and 14C-adenosine (14C-ADO) was significantly (p < 0.005) increased using 0.01 mM H2O2. Only an increase of 14C-ADO incorporation was observed using 0.1 mM H2O2. A concentration of 0.01 mM H2O2 reduced 5-phosphoribosyl-1-pyrophosphate synthetase (PRPP-S) activity by 60% and at the same time increased the activity of purine nucleoside phosphorylase, which converts inosine to hypoxanthine (PNP I), by 24%. Adenosine kinase (AK) activity was reduced by H2O2, whereas adenine phosphoribosyltransferase (APRT) activity was found to be elevated. In conclusion, the observed elevation of cellular ATP and CP levels could be partially caused by an increased purine salvage resulting from changes in purine enzyme activities.
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PMID:The H2O2 induced effects on purine metabolism in human endothelial cells. 813 86

Chronic exposure (>200 days) of HA1 fibroblasts to increasing concentrations of H2O2 or O2 results in the development of a stable oxidative stress-resistant phenotype characterized by increased cellular antioxidant levels, particularly catalase (D. R. Spitz et al, Arch. Biochem. Biophys., 279: 249-260, 1990; D. R. Spitz et al., Arch. Biochem. Biophys., 292: 221-227, 1992; S. J. Sullivan et al., Am. J. Physiol. (Lung Cell. Mol. Physiol.), 262: L748-L756, 1992). Acutely stressed cells failed to develop a stably resistant phenotype or increased catalase activity, suggesting that chronic exposure is required for the development of this phenotype. This study investigates the mechanism underlying increased catalase activity in the H2O2- and O2-resistant cell lines. In H2O2- and O2-resistant cells, catalase activity was found to be 20-30-fold higher than that in the parental HA1 cells and correlated with increased immunoreactive catalase protein and steady-state catalase mRNA levels. Resistant cell lines also demonstrated a 4-6-fold increase in catalase gene copy number by Southern blot analysis, which is indicative of gene amplification. Chromosome banding and in situ hybridization studies identified a single amplified catalase gene site located on a rearranged chromosome with banding similarities to Z-4 in the hamster fibroblast karyotype. Simultaneous in situ hybridization with a Z-4-specific adenine phosphoribosyltransferase (APRT) gene revealed that the amplified catalase genes were located proximate to APRT on the same chromosome in all resistant cells. In contrast, HA1 cells contained only single copies of the catalase gene that were not located on APRT-containing chromosomes, indicating that amplification is associated with a chromosomal rearrangement possibly involving Z-4. The fact that chronic exposure of HA1 cells to either HO2 or 95% O2 resulted in gene amplification suggests that gene amplification represents a generalized response to oxidative stress, contributing to the development of resistant phenotypes. These results support the hypothesis that chronic exposure to endogenous metabolic or exogenous environmental oxidative stress represents an important factor contributing to gene amplification and genomic instability.
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PMID:Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. 973 12