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)

The pathogenesis of O2 toxicity involves intracellular production of partially reduced O2 metabolites, which increases with O2 partial pressure. Cytotoxic O2 metabolites impair enzyme function and inhibit DNA, protein, and surfactant lipid biosynthesis. Compounds used clinically that increase O2 metabolism or that are metabolized through free radical intermediates may increase pulmonary O2 toxicity. Recent development of liposome-encapsulated and polyethylene glycol-conjugated antioxidant enzyme preparations may provide a clinically useful means of minimizing O2 toxicity and other oxidant injuries. Human pulmonary O2 toxicity is characterized initially by acute edematous lung injury followed by fibrosis and pulmonary hypertension. Functional changes due to O2 toxicity include diffusion impairment, worsening of ventilation/perfusion relationships, decreased lung compliance, and small airways dysfunction. It is likely that new data derived from molecular and cellular studies of O2 toxicity will continue to enrich the clinical atmosphere and allow more directed approaches to therapy of acute lung injuries, including ARDS.
 ...
PMID:Molecular, pharmacologic, and clinical aspects of oxygen-induced lung injury. 218 80

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.
 ...
PMID:The nature of antioxidant defense mechanisms: a lesson from transgenic studies. 978 1