Glutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury.
In this study we examined the role of the antioxidant glutathione (GSH) in pulmonary susceptibility to ozone toxicity, utilizing GSH deficient C57BL/6J mice that lack the expression of glutamate-cysteine ligase modifier subunit (GCLM). Gclm(-/-) knockout mice had 70% GSH depletion in the lung. Gclm(+/+) wild-type and Gclm(-/-) mice were exposed to either 0.3 ppm ozone or filtered air for 48h. Ozone-induced lung hyperpermeability, as measured by total protein concentration in bronchoalveolar lavage fluid, was surprisingly lower in Gclm(-/-) mice than in wild-type mice. Lung hyperpermeability did not correlate with the degree of neutrophilia or with inflammatory gene expression. Pulmonary antioxidant response to ozone, assessed by increased mRNA levels of metallothionein 1 and 2, alpha-tocopherol transporter protein, and solute carrier family 23 member 2 (sodium-dependent vitamin C transporter) was greater in Gclm(-/-) mice than in Gclm(+/+) mice. These results suggest that compensatory augmentation of antioxidant defenses in Gclm(-/-) mice may confer increased resistance to ozone-induced lung injury.
Johansson
Elisabet
E
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA. johanse@email.uc.edu
Wesselkamper
Scott C
SC
Shertzer
Howard G
HG
Leikauf
George D
GD
Dalton
Timothy P
TP
Chen
Ying
Y
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000172:deficiency* / Q000235:genetics; D008168:Lung / Q000187:drug effects; D055370:Lung Injury / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010126:Ozone / Q000009:adverse effects*; D011014:Pneumonia / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D010126:Ozone; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione