ANTAGONISTIC EFFECTS OF PYRROLIDINE DITHIOCARBAMATE AND N-ACETYL-L-CYSTEINE ON SURFACTANT PROTEIN A AND B mRNAs

Pulmonary surfactant, a mixture of phospholipids and specific associated proteins, reduces surface tension at the air-liquid interface of the lung and protects the large epithelial surface of the lung from infectious organisms. Surfactant proteins, SP-A and SP-B, are required for normal surfactant f...

Full description

Saved in:
Bibliographic Details
Published in:Experimental lung research 1999, Vol.25 (6), p.479-493
Main Author: Rubia Khalak, Heidie L. Huyck, Gloria S. Pryhuber
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Apolipoprotein j
Epithelium
Glutathione
Lung
Oxidant Stress
Surfactant
Biological and medical sciences
Blotting, Northern
Carmustine - pharmacology
Cell Line
Clusterin
Drug Synergism
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gene Expression Regulation
Glutathione - metabolism
Glutathione Disulfide - metabolism
Glutathione Reductase - antagonists & inhibitors
Glycoproteins - drug effects
Glycoproteins - genetics
Glycoproteins - metabolism
Humans
Hydrogen Peroxide - pharmacology
Lung - drug effects
Lung - metabolism
Medical sciences
Molecular Chaperones
Pharmacology. Drug treatments
Proteolipids - antagonists & inhibitors
Proteolipids - biosynthesis
Proteolipids - genetics
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - antagonists & inhibitors
Pulmonary Surfactants - biosynthesis
Pulmonary Surfactants - genetics
Pyrrolidines - pharmacology
Respiratory system
Ribonucleases - metabolism
RNA, Messenger - antagonists & inhibitors
RNA, Messenger - metabolism
Thiocarbamates - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pulmonary surfactant, a mixture of phospholipids and specific associated proteins, reduces surface tension at the air-liquid interface of the lung and protects the large epithelial surface of the lung from infectious organisms. Surfactant proteins, SP-A and SP-B, are required for normal surfactant function. In the current work, increased levels of oxidized glutathione (GSSG) are demonstrated at doses of pyrrolidine dithiocarbamate (PDTC) which decrease SP-A and SP-B mRNAs, suggesting that cellular oxidation reduces surfactant protein expression. Similarly, reduction of SP-A and SP-B mRNA levels following accumulation of GSSG induced by glutathione reductase inhibitor 1, 3-bis-(2-chloroethyl)-1 nitrosourea (BCNU), supports the hypothesis that surfactant protein synthesis is reduced in response to oxidation of pulmonary epithelial glutathione. Concurrent induction of apolipoprotein J(apoJ) mRNA by PDTC demonstrates the selectivity of pulmonary gene regulation by the dithiocarbamate. In contrast, the glutathione precursor N-acetyl-l-cysteine (NAC) prevented PDTC-dependent increase in GSSG/GSH ratio, inhibition of SP-A and -B mRNAs, and induction of apoJ. Insufficiency of SP-A and -B, which occurs in inflammatory lung diseases, may result from the exposure of the pulmonary epithelium to oxidant stress and may be reversed by the antioxidant NAC.
ISSN:0190-2148
1521-0499
DOI:10.1080/019021499270088