Studies on the inhibition of collagen synthesis in fibroblasts treated with paraquat.
Paraquat (methyl viologen) is an industrial herbicide which upon entering many cell types can be enzymatically reduced and in the presence of oxygen, subsequently generate the superoxide radical anion (O2-). This is its mode of toxicity in many of these cells. In vivo, it has been shown to preferentially accumulate in lung tissue, leading to tissue destruction and marked fibrosis. Collagen accumulation has also been noted in paraquat-treated lung slices in vitro. In studies designed to investigate these effects, it has been found, unexpectedly, that paraquat inhibits collagen synthesis in isolated fibroblasts. This inhibition is not due to overt cellular toxicity nor to inhibition of prolyl hydroxylase (directly or by cofactor depletion). While this effect could be unique to paraquat, it may be relevant to a more generalized role for free radicals in regulating collagen synthesis at the level of the individual cell.
Darr
D
D
Duke University Medical Center, Division of Dermatology, Durham, North Carolina 27710.
Combs
S
S
Murad
S
S
Pinnell
S
S
D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010269:Paraquat / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D003094:Collagen; D010269:Paraquat; D001205:Ascorbic Acid