Monocrotaline alters type II pneumocyte morphology and polyamine regulation.
Lungs from monocrotaline (MCT)-treated rats exhibit altered polyamine metabolism and content. One of the prominent morphological abnormalities in MCT-treated lungs is a decrease in population density of type II pneumocytes. Against this background, the present study tested the hypothesis that failure to maintain normal population density of type II pneumocytes is associated with MCT-induced derangements in polyamine biosynthesis and/or transmembrane polyamine transport. After a 24-hr treatment, cultured type II pneumocytes exhibited numerous vacuoles at the highest dose of 3.2 mM MCT but not at the lower dose of 1.6 mM MCT. Intracellular spermidine content was significantly reduced at the highest dose of MCT. Relative to controls, the abundance of mRNA for both ornithine decarboxylase, and S-adenosylmethionine decarboxylase, key regulatory enzymes in polyamine synthesis, was not altered. However, the activities of both of these enzymes were dramatically reduced. Increased mRNA for the catabolic polyamine enzyme, spermine/spermidine-N1-acetyltransferase (SAT), paralleled significant increases in SAT activity. MCT also caused a concentration-related inhibition of spermidine uptake in type II cells, characterized by a fourfold decrease in Vmax with little change in Km. These results show that MCT alters type II pneumocyte polyamine regulatory mechanisms and may help explain the decreased population density of type II pneumocytes in MCT-treated rats.
Baybutt
R C
RC
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Aziz
S M
SM
Fagerland
J A
JA
Olson
J W
JW
Gillespie
M N
MN
D000123:Acetyltransferases / Q000378:metabolism; D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D002478:Cells, Cultured; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D016686:Monocrotaline / Q000633:toxicity*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013095:Spermidine / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D012437:Adenosylmethionine Decarboxylase; D015317:Biogenic Polyamines; D016686:Monocrotaline; D009955:Ornithine Decarboxylase; D013095:Spermidine; D000099228:Diamine N-Acetyltransferase