Rapid degradation of PrxI and PrxII induced by silica in Rat2 cells.
Peroxidases of the peroxiredoxin (Prx) family catalyze the reduction of H(2)O(2) and lipid peroxides. The effects of H(2)O(2), 12-O-tetradecanoylphorbol 13-acetate (TPA), and silica on the abundance of two cytosolic isoforms of Prx (PrxI and PrxII) were examined in Rat2 cells. TPA induces the production of reactive oxygen species (ROS) in various mammalian cell types, and silica induces the production of ROS in Rat2 cells. Whereas H(2)O(2) and TPA did not affect the concentration of PrxI or Prx II, silica triggered a rapid degradation of both Prx enzymes. Silica also induced degradation of the NF-kappaB inhibitor IkappaB-alpha. N-Acetylcysteine and diphenyleneiodonium, both of which inhibit the accumulation of intracellular ROS, each blocked silica-induced degradation of IkappaB-alpha but had no effect on that of the Prx enzymes, suggesting that ROS do not contribute to Prx proteolysis. The silica-induced degradation of Prx enzymes was also insensitive to the proteasome inhibitors MG132 and lactacystin, whereas IkappaB-alpha proteolysis was completely blocked by these inhibitors. Experiments with the Ca(2+) ionophore A23187 indicated that a Ca(2+)-dependent protease such as calpain might contribute substantially to silica-induced degradation of PrxII, but only moderately to that of PrxI. These results indicate that silica increases cellular oxidative stress not only by inducing ROS production, but also by triggering the degradation of Prx enzymes that are responsible for elimination of cellular ROS. Such aggravated oxidative stress might be important in the initial pathogenesis of silica-associated pulmonary diseases.
Seo
M S
MS
College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.
Kim
J K
JK
Lim
Y
Y
Kang
S W
SW
Cho
Y J
YJ
Lee
W K
WK
Kim
H J
HJ
Cho
K K
KK
Lee
K H
KH
Rhee
S G
SG
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020672:I-kappa B Proteins; D007476:Ionophores / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D018384:Oxidative Stress / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000975:Antioxidants; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007476:Ionophores; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D017382:Reactive Oxygen Species; D000072000:NF-KappaB Inhibitor alpha; D000001:Calcimycin; D012822:Silicon Dioxide; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D013755:Tetradecanoylphorbol Acetate