Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress.
MER5 (also called peroxiredoxin III, PrxIII) is a member of peroxiredoxin family that has antioxidant activity. The present study was performed to investigate its in vivo function using MER5 knockout mice. MER5 knockout mice were born in normal frequency and could grow to maturity, but we found that intracellular ROS levels are significantly higher in the macrophages of the knockout mice. We examined roles of MER5 function for the oxidative stress responses by intratracheal inoculation of lipopolysaccharide (LPS) to the mice. Lung inflammation such as inflammatory cell infiltration and airway wall thickening was more severely detected in the knockout mice. At the same time, oxidative damage on DNA and proteins was more strongly detected in lung tissues of the knockout mice, including 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and protein carbonylation. The degrees of lung inflammation and oxidative damage were positively related with LPS doses. Our results indicate that MER5 knockout mice accumulated higher intracellular ROS levels, which cause LPS-induced lung injury more severely, and thus, suggested that MER5 acts as an important scavenger of reactive oxygen species (ROS) under oxidative stress.
Li
Lianqin
L
Department of Cell Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seriyo-machi, Aoba-ku, Sendai 980-8575, Japan.
Shoji
Wataru
W
Takano
Hirohisa
H
Nishimura
Noriko
N
Aoki
Yasunobu
Y
Takahashi
Ryoya
R
Goto
Sataro
S
Kaifu
Tomonori
T
Takai
Toshiyuki
T
Obinata
Masuo
M
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics*; D010544:Peroxidases / Q000235:genetics / Q000502:physiology*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism
D008070:Lipopolysaccharides; C516116:Prdx3 protein, mouse; D011506:Proteins; D017382:Reactive Oxygen Species; D004247:DNA; D010544:Peroxidases; D061105:Peroxiredoxin III; D054464:Peroxiredoxins