Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxic lung injury is an unfortunate consequence of ventilatory oxygen therapy that is necessary to sustain life in certain clinical situations. The biochemical events that accompany hyperoxia of the lung, and the molecular mechanisms underlying these events, are incompletely understood. To better understand hyperoxic lung injury, our laboratory has cloned a set of genes corresponding to mRNAs that increase in abundance in the lungs of hyperoxic rabbits. In this report, we focus on three hyperoxia-induced cDNA clones, which encode surfactant apoprotein A (SP-A), the tissue inhibitor of metalloproteinases (TIMP), and metallothionein. In situ hybridizations and RNA dot blots of isolated lung cell populations indicate that the abundance of mRNA encoding all three proteins is increased by hyperoxia in specific cell types. SP-A mRNA increases in type II alveolar epithelial cells and in bronchiolar epithelial cells. TIMP mRNA increases in interstitial fibroblasts, in chondrocytes of the cartilage surrounding airways, and in endothelial cells of a specific subset of vessels, probably venules. Metallothionein transcripts also increase in chondrocytes and pulmonary fibroblasts. A comparison of the increase in these mRNAs during hyperoxic exposure in adults and newborns indicates that adults respond faster and to a greater extent than newborns and suggests that the rate and extent of these increases is correlated with the time course and severity of the injury.
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PMID:Cell-specific alterations in expression of hyperoxia-induced mRNAs of lung. 195 78

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein with extensive metal binding capacity and potential nonenzymatic antioxidant activity. Despite the sensitivity of vascular endothelium to either heavy metal toxicity or oxidative stress, little is known regarding the role of MT in endothelial cells. Accordingly, we determined the sensitivity of cultured sheep pulmonary artery endothelial cells (SPAEC) that overexpressed MT to tert-butyl hydroperoxide (t-BOOH), hyperoxia, or 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN; peroxyl radical generator). Nontoxic doses of 10 microM Cd increased MT levels from 0.21 +/- 0.03 to 2.07 +/- 0.24 microg/mg and resulted in resistance to t-BOOH and hyperoxia as determined by reduction of Alamar blue or [3H]serotonin transport, respectively. SPAEC stably transfected with plasmids containing either mouse or human cDNA for MT were resistant to both t-BOOH and hyperoxia. In addition, we examined transition metal-independent, noncytotoxic AMVN-induced lipid peroxidation after metabolic incorporation of the oxidant-sensitive fluorescent fatty acid cis-parinaric acid into phospholipids and high-performance liquid chromatography separation. SPAEC that overexpressed MT after gene transfer completely inhibited peroxyl oxidation of phosphatidylserine, phosphatidylcholine, and sphingomyelin (but not phosphatidylethanolamine) noted in wild-type SPAEC. These data show for the first time that MT can 1) protect pulmonary artery endothelium against a diverse array of prooxidant stimuli and 2) directly intercept peroxyl radicals in a metal-independent fashion, thereby preventing lipid peroxidation in intact cells.
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PMID:Overexpression of metallothionein decreases sensitivity of pulmonary endothelial cells to oxidant injury. 935 62

Metallothionein (MT) is a small, cysteine-rich, metal-binding protein. MT synthesis is induced by various stimuli such as heavy metals, oxidative stress, anticancer drugs and fasting stress. MT is capable of not only reducing metal toxicity but also scavenging free radicals. In fact, MT is involved in the protection of tissues against various forms of oxidative injury, including radiation, lipid peroxidation, oxidative stress caused by anticancer drugs, and conditions of hyperoxia. However, MT still lacks a manifest established biological function. Recently, transgenic mice with loss-of-function mutations in the MT-I/-II genes were established. Unexpectedly, the mice were in apparent good health, and the critical biological roles for MT have been questioned. Here the basic characteristics of MT are reviewed, the current MT study highlights summarized, and the putative biological functions of MT discussed.
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PMID:[Protective stress responsive protein: metallothionein]. 1186 93

Metallothionein (MT) is a ubiquitous, cysteine-rich, metal-binding protein. MT synthesis is induced by various stimuli such as cadmium, mercury, zinc, oxidative stress, glucocorticoid, and anticancer agents. Recently, transgenic mice with loss-of-function mutations in the MT-I/-II genes were established. It has been assumed that MT plays a role in the detoxification of heavy metals. In recent studies using MT-null mice, the ability of MT to protect against cadmium-induced renal, liver and bone injuries has been confirmed. Moreover, MT is also capable of scavenging oxygen free radicals. MT is involved in the protection of tissues against various forms of oxidative injury, including radiation, lipid peroxidation, oxidative stress caused by anticancer drugs, and conditions of hyperoxia. However, MT still lacks an established biological function. Unexpectedly, the MT-null mice were apparently in good health, and the critical biological roles of MT have been questioned. MT seems to be a protective protein produced in response to a variety of stresses. Here, current studies on the protective roles of MT against toxicity of heavy metals and reactive oxygen species are reviewed, and the putative biological functions of MT are discussed.
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PMID:Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals. 1249 22