Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This hypothesis states that magnesium and copper (Cu) deficiency as well as high arterial oxygen pressure may contribute to the pathogenesis of retinopathy of prematurity (ROP), a major cause of blindness in very low birthweight preterm infants. Infants at highest risk have severe respiratory distress with hypoxia and require prolonged oxygen supplements. The retina is a multilayer sheet of neural tissue very rich in polyunsaturated fatty acids (PUFAs), oxygen, and mitochondria, with the highest oxygen consumption of all body tissues. Oxygen free radicals which are generated during metabolism cause lipid peroxidation of the PUFA-rich membranes, impairing retinal function. Magnesium and copper deficiencies provide less protection from oxidative injury which damages neurosensory tissue critical for photodetection. Protective antioxidant enzyme activity is reduced in magnesium and copper deficiency. There is some evidence for a raised level of vasoconstrictor thromboxane A2 (TXA2) in respect to vasodilator prostacyclin (PGI2), which would promote vasoconstriction. Deficiency of magnesium and of copper increase synthesis of TXA2 and decreases synthesis of PGI2. Sustained vasoconstriction leads to vascular occlusion, retinal ischaemia, reactive proliferation of retinal vasculature, and the final stages of ROP. Abundant magnesium and copper may protect the retina from developing ROP.
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PMID:Hypothesis: the possible role of magnesium and copper deficiency in retinopathy of prematurity. 884 91

The relevance of prostanoids to inflammation, thrombosis, and cardiovascular diseases is well known. The present study attempts to explore age effects on prostanoids and their biosynthesis cascade. Results from comparing prostanoid levels between young (6 months) and old (24 months) Fischer 344 rats showed rises of prostaglandin E2 (PGE2), PGI2, and thromboxane A2 (TXA2) levels in the old rats. Correlating evidence showed gene expression up-regulation of several prostanoid synthase enzymes in old rat aorta. Further, we found that expression of the antioxidant enzyme glutathione peroxidase was raised by age in the aorta, while superoxide dismutase and catalase expression showed no significant change during aging in the aorta. Moreover, calorie restriction (CR) was found to attenuate age-related prostanoid changes by suppressing inflammatory activities. In conclusion, the data from this study indicated that age-related increases in prostanoids and their biosynthesis might be closely associated with a weakened antioxidant capacity.
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PMID:Vascular aging: molecular modulation of the prostanoid cascade by calorie restriction. 1547 49

Exposure of human umbilical endothelial cells (ECs) to cigarette smoke extract (CSE) activated the NADPH-oxidase enzyme and increased the production of superoxide (O-2) as well as reactive oxygen species (ROS). CSE also inhibited the prostacyclin (PGI2) formation by ECs. Preincubation of ECs with diphenylene iodonium (DPI), the inhibitor of NADPH oxidase, blocked the increase of O-2 production, but neither lowered the ROS level nor prevented the inhibition of PGI2 formation in CSE-treated cells. Preincubation of ECs with a medium supplemented with 1 mM vitamin C did not decrease, but rather increased the O-2 production in CSE-treated cells. However, adding 1 mM glutathione (GSH) to vitamin C decreased the O-2 production, indicating that vitamin C was overwhelmed by the prooxidant in CS, and GSH enhanced the recycling process and spared vitamin C. The ROS level remained high in CSE-treated cells even after preincubation with vitamin C or vitamin C + GSH compared to the control cells. These results are discussed in light of the possible decrease of antioxidant enzyme activities in CSE-treated cells and the increase of cellular hydrogen peroxide (H2O2) generated from the CSE, which cause an imbalance between oxidizing species and the antioxidants producing oxidative stress in CSE-treated cells. These results demonstrate that CSE has a direct inhibitory effect on PGI2 formation and enhances the level of ROS in CSE-treated ECs, regardless of the activation of NADPH-oxidase.
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PMID:Inhibition of prostacyclin release by cigarette smoke extract in endothelial cells is not related to enhanced superoxide generation and NADPH-oxidase activation. 1707 61

Cyclooxygenase (COX)-2 is among the endothelial genes upregulated by uniform laminar shear stress (LSS), characteristically associated with atherosclerotic lesion-protected areas. We have addressed whether the induction of COX-2-dependent prostanoids in endothelial cells by LSS plays a role in restraining endothelial tumor necrosis factor (TNF)-alpha generation, a proatherogenic cytokine, through the induction of heme oxygenase-1 (HO)-1, an antioxidant enzyme. In human umbilical vein endothelial cells (HUVECs) exposed to steady LSS of 10 dyn/cm(2) for 6 hours, COX-2 protein was significantly induced, whereas COX-1 and the downstream synthases were not significantly modulated. This was associated with significant (P<0.05) increase of 6-keto-prostaglandin (PG)F(1alpha) (the hydrolysis product of prostacyclin), PGE(2), and PGD(2). In contrast, TNF-alpha released in the medium in 6 hours (3633+/-882 pg) or detected in cells lysates (1091+/-270 pg) was significantly (P<0.05) reduced versus static condition (9100+/-2158 and 2208+/-300 pg, respectively). Coincident induction of HO-1 was detected. The finding that LSS-dependent reduction of TNF-alpha generation and HO-1 induction were abrogated by the selective inhibitor of COX-2 NS-398, the nonselective COX inhibitor aspirin, or the specific prostacyclin receptor (IP) antagonist RO3244794 illuminates the central role played by LSS-induced COX-2-dependent prostacyclin in restraining endothelial inflammation. Carbacyclin, an agonist of IP, induced HO-1. Similarly to inhibition of prostacyclin biosynthesis or activity, the novel imidazole-based HO-1 inhibitor QC15 reversed TNF-alpha reduction by LSS. These findings suggest that inhibition of COX-2-dependent prostacyclin might contribute to acceleration of atherogenesis in patients taking traditional nonsteroidal antiinflammatory drugs (NSAIDs) and NSAIDs selective for COX-2 through downregulation of HO-1, which halts TNF-alpha generation in human endothelial cells.
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PMID:Induction of prostacyclin by steady laminar shear stress suppresses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells. 1912 75