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J Biol Chem, Vol. 274, Issue 48, 33881-33887, November 26, 1999
Signaling in Activated Rat Hepatic
Stellate Cells
,,,
From the Reactive oxygen species are implicated in the
pathogenesis of several diseases, including Alzheimer's disease,
multiple sclerosis, human immunodeficiency virus, and liver fibrosis.
With respect to liver fibrosis, we have investigated differences in
antioxidant enzymes expression in stellate cells (SCs) and parenchymal
cells from normal and CCl4-treated rat livers. We
observed an increase in the expression of catalase in activated SCs.
Treatment with transforming growth factor- Laboratory for Cell Biology and Histology
and § Laboratory for Toxicology, Free University Brussels,
B-1090 Brussels, Belgium
(TGF-) increased the
production of H2O2. Treatment with catalase
decreased TGF- expression. Addition of H2O2
resulted in increased TGF- production. 3-Amino-1,2,4-triazole abolished the capacity of SCs to remove H2O2. A
paradoxical increase in capacity was observed when the cells were
pretreated with diethyl maleate. Treatment with 3-amino-1,2,4-triazole
increased TGF- production. A paradoxical decrease of TGF-
production was observed with diethyl maleate. Treatment of the cells
with N-acetylcysteine resulted in increased TGF-
production. TGF- decreased the capacity of the SCs to remove
H2O2. An increase in the capacity to remove H2O2 was observed when TGF- was removed by
neutralizing antibodies. In conclusion, our results suggest: 1) a link
between cellular GSH levels and TGF- production and 2) that cellular
GSH levels discriminate whether H2O2 is the
result of oxidative stress or acts as second messenger in the TGF-
signal transduction pathway.
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