Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-toxin, the major cytotoxic agent elaborated by Staphylococcus aureus, was the first bacterial exotoxin to be identified as a pore former. The protein is secreted as a single-chain, water-soluble molecule of Mr 33,000. At low concentrations (less than 100 nM), the toxin binds to as yet unidentified, high-affinity acceptor sites that have been detected on a variety of cells including rabbit erythrocytes, human platelets, monocytes and endothelial cells. At high concentrations, the toxin additionally binds via nonspecific absorption to lipid bilayers; it can thus damage both cells lacking significant numbers of the acceptor and protein-free artificial lipid bilayers. Membrane damage occurs in both cases after membrane-bound toxin molecules collide via lateral diffusion to form ring-structured hexamers. The latter insert spontaneously into the lipid bilayer to form discrete transmembrane pores of effective diameter 1 to 2 nm. A hypothetical model is advanced in which the pore is lined by amphiphilic beta-sheets, one surface of which interacts with lipids whereas the other repels apolar membrane constitutents to force open an aqueous passage. The detrimental effects of alpha-toxin are due not only to the death of susceptible targets, but also to the presence of secondary cellular reactions that can be triggered via Ca2+ influx through the pores. Well-studied phenomena include the stimulation of arachidonic acid metabolism, triggering of granule exocytosis, and contractile dysfunction. Such processes cause profound long-range disturbances such as development of pulmonary edema and promotion of blood coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-toxin of Staphylococcus aureus. 177 33

beta-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na(+) channels (ENaC) and Na,K-ATPases. Here we report that adenoviral-mediated overexpression of a human beta(2)-adrenergic receptor (beta(2)AR) cDNA increases beta(2)AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na(+) transport and increased abundance of Na,K-ATPases in the basolateral cell membrane. beta(2)AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound beta(2)AR expression and function and increased levels of ENaC (alpha subunit) abundance and Na,K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na(+) transport, in beta(2)AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the beta(2)AR-specific agonist procaterol to beta(2)AR overexpressing lungs did not increase AFC further. AFC in beta(2)AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar beta(2)AR overexpression improves beta(2)AR function and maximally upregulates beta-agonist-responsive active Na(+) transport by improving responsiveness to endogenous catecholamines. These studies suggest that upregulation of beta(2)AR function may someday prove useful for the treatment of pulmonary edema.
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PMID:beta(2)-adrenergic receptor overexpression increases alveolar fluid clearance and responsiveness to endogenous catecholamines in rats. 1170 18

beta-Adrenergic receptor (betaAR) agonists accelerate the clearance of edema from the alveolar airspace by increasing the function of epithelial transport proteins, including epithelial Na(+) channels and Na,K-adenosinetriphosphatases. To improve our understanding of the role of the beta(2)AR in regulating alveolar fluid clearance, we used an adenoviral-mediated gene transfer strategy to effect significant increases in membrane-bound beta(2)AR number and function in the alveolar epithelium of normal rats. Alveolar fluid clearance in beta(2)AR-overexpressing lungs, measured by means of an isolated lung model in the absence of catecholamine supplementation, was 100% greater than in controls. These findings were associated with significant increases of epithelial Na(+) channel function and Na,K-adenosine triphosphatase function in the peripheral lung. Experiments performed with adrenalectomized rats, a beta(2)-agonist (procaterol), and a nonspecific beta-antagonist (propranolol) indicate that overexpression maximally up-regulates beta(2)-adrenergic-responsive alveolar fluid clearance and improves responsiveness to endogenous catecholamines. Mechanistic studies in human lung epithelial cells (A549) indicate that receptor overexpression prevents homologous receptor desensitization, possibly by overwhelming endogenous regulatory pathways. Our studies demonstrate that overexpression of beta(2)AR in lung epithelial cells can be used to study the role and regulation of alveolar beta(2)ARs. They also suggest a therapeutic role for the beta(2)AR in the treatment of pulmonary edema.
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PMID:Effects of beta2-adrenergic receptor overexpression on alveolar epithelial active transport. 1246 31