R. Khalak et al., Antagonistic effects of pyrrolidine dithiocarbamate and N-acetyl-L-cysteine on surfactant protein A and B mRNAs, EXP LUNG R, 25(6), 1999, pp. 479-493
Pulmonary surfactant, a mixture of phospholipids and specific associated pr
oteins, reduces surface tension at the air-liquid interface of the lung and
protects the large epithelial surface of the lung from infectious organism
s. Surfactant proteins, SP-A and SP-B, are required for normal surfactant f
unction. In the current work, increased levels of oxidized glutathione (GSS
G) are demonstrated at doses of pyrrolidine dithiocarbamate (PDTC) which de
crease SP-A and SP-B mRNAs, suggesting that cellular oxidation reduces surf
actant protein expression. Similarly, reduction of SP-A and SP-B mRNA level
s 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 pulmon
ary 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-cyst
eine (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 o
f the pulmonary epithelium to oxidant stress and may be reversed by the ant
ioxidant NAC.