Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family in which a Pinull allele for alpha-1-antitrypsin (A-1-AT) segregates has been studied in detail. Two homozygous sisters have no detectable A-1-AT in their serum as measured with the most sensitive methods currently available. Both have airways obstruction, and one has bullous emphysema. Heterozygotes for Pinull and the common normal allele PiM1 have half-normal serum concentrations of A-1-AT. A restriction enzyme analysis of chromosomal DNA of the two homozygotes and one heterozygote demonstrated the presence of an apparently complete structural gene for A-1-AT. Thus, the genetic defect in Pinull is not a complete or partial deletion of the structural gene. A base pair change that cannot be detected by the restriction enzymes used here, of course, cannot be excluded. Another possibility is a mutation outside the structural gene that affects the synthesis of the protein.
 ...
PMID:Complete absence of serum alpha-1-antitrypsin in conjunction with an apparently normal gene structure. 301 71

Chronic inflammation, oxidative stress, and proteolysis participate primarily in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. COPD is a highly prevalent smoking-related disease for which no effective therapy exists to improve the disease course. Although apolipoprotein A-1 (ApoA1) has antiinflammatory and antioxidant properties as well as cholesterol efflux potential, its role in cigarette smoke (CS)-induced emphysema has not been determined. Therefore, we investigated whether human ApoA1 transgenic (TG) mice, with conditionally induced alveolar epithelium to overexpress ApoA1, are protected against the CS-induced lung inflammatory response and development of emphysema. In this study, ApoA1 levels were significantly decreased in the lungs of patients with COPD and in the lungs of mice exposed to CS. ApoA1 TG mice did not develop emphysema when chronically exposed to CS. Compared with the control TG mice, ApoA1 overexpression attenuated lung inflammation, oxidative stress, metalloprotease activation, and apoptosis in CS-exposed mouse lungs. To explore a plausible mechanism of antiapoptotic activity of ApoA1, alveolar epithelial cells (A549) were treated with CS extract (CSE). ApoA1 prevented CSE-induced translocation of Fas and downstream death-inducing signaling complex into lipid rafts, thereby inhibiting Fas-mediated apoptosis. Taken together, the data showed that ApoA1 overexpression attenuated CS-induced lung inflammation and emphysema in mice. Augmentation of ApoA1 in the lung may have therapeutic potential in preventing smoking-related COPD/emphysema.
 ...
PMID:Attenuation of Cigarette Smoke-Induced Emphysema in Mice by Apolipoprotein A-1 Overexpression. 2608 25