Differential expression of EC-SOD, Mn-SOD and CuZn-SOD in rat lung exposed to crystalline silica.
Superoxide dismutases (SODs) are antioxidant enzymes that catalyze the dismutation of superoxide into hydrogen peroxide. There are 3 kinds of isozymes: extracellular superoxide dismutase (EC-SOD), manganese-containing superoxide dismutase (Mn-SOD) and copper- and zinc-containing superoxide dismutase (CuZn-SOD). To examine the expression of SOD isozymes in lungs injured by crystalline silica, we intratracheally instilled male Wistar rats with 2 mg (8 mg/kg) of crystalline silica and investigated the mRNA, protein level and distribution of SOD isozymes in the rat lungs using RT-PCR, western blot analysis and immunostaining, respectively at from 3 d to 180 d of recovery following the exposure. EC-SOD mRNA levels significantly increased from 3 d to 90 d and the EC-SOD protein level was significantly higher after 90 and 180 d recovery in the crystalline silica exposed groups than in the control groups. Mn-SOD increased in silica treated rat lungs at both mRNA and protein levels, peaking at 30 d post-exposure. CuZn-SOD mRNA levels were decreased at 3, 7 and 30 d, and CuZn-SOD protein levels were also significantly lower than the control group at 90 and 180 d recovery. There was prominent EC-SOD immunostaining mainly in the plasma and alveolar macrophages and strong Mn-SOD staining in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following crystalline silica exposure. There was less CuZn-SOD staining in epithelial cells at terminal bronchioles in the crystalline silica-exposed group. These findings suggest that these SOD isozymes may be related to lung injury induced by crystalline silica.
Kim
Heungnam
H
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA.
Morimoto
Yasuo
Y
Ogami
Akira
A
Nagatomo
Hiroko
H
Hirohashi
Masami
M
Oyabu
Takako
T
Kawanami
Yukiko
Y
Kuroda
Etsushi
E
Higashi
Toshiaki
T
Tanaka
Isamu
I
D000818:Animals; D007564:Japan; D008168:Lung / Q000201:enzymology*; D055370:Lung Injury; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000032:analysis* / Q000378:metabolism
D012822:Silicon Dioxide; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase