Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages.
We previously reported cDNA cloning of a novel oxidative stress protein termed A170 from murine macrophages. Further experiments have demonstrated that exposure of the cells to low levels of H2O2 produced by glucose/glucose oxidase markedly induced the 60-kDa A170 protein. This result suggests that the level of A170 protein can also be controlled at posttranscriptional levels, because we showed previously that H2O2 hardly increased the level of A170 mRNA. We have found that proteasome inhibitors markedly induced the A170 protein after 2 to 8 h similarly to glucose/glucose oxidase, suggesting rapid degradation of the A170 protein by proteasome under normal conditions. Activation of cellular signaling pathways either by epidermal growth factor, lipopolysaccharide or tumor necrosis factor-alpha did not enhance the level of the A170 protein. The levels of glucose oxidase-induced A170 protein did not decrease after the addition of cycloheximide. These results suggest that low levels of H2O2 may stabilize the A170 protein, allowing it to accumulate within cells.
Ishii
T
T
Department of Biochemistry, University of Tsukuba, Ibaraki, Japan. teishii@md.tsukuba.ac.jp
Yanagawa
T
T
Yuki
K
K
Kawane
T
T
Yoshida
H
H
Bannai
S
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005949:Glucose Oxidase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D015853:Cysteine Proteinase Inhibitors; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D011494:Protein Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex