Protective role of peroxisome proliferator-activated receptor β/δ in acute lung injury induced by prolonged hyperbaric hyperoxia in rats.
Peroxisome proliferator-activated receptor (PPAR)-β/δ is a transcription factor that belongs to the PPAR family, but the role of PPAR-β/δ in acute lung injury (ALI) induced by hyperbaric oxygen is unknown. In this study we investigated if PPAR-β/δ activation protects from hyperoxia-induced ALI in a rat model. ALI was induced by prolonged hyperbaric oxygen (HBO2) (2.3ATA, 100% O2) for 8h. Administration of PPAR-β/δ agonist GW0742 (0.3mg/kg, i.p.) at 1 and 6h prior to HBO2 exposure significantly reduced the (1) lung injury, (2) proinflammatory cytokines (TNF-α, IL-1β, IL-6), (3) apoptosis (Bax/Bcl-2, cleaved-caspase-3 and TUNEL), (4) nuclear factor (NF)-κB expression level and DNA binding activity in the nucleus, and (5) extracellular signal-regulated kinase (ERK)1/2 phosphorylation and markedly elevated (6) superoxide dismutase and glutathione peroxidase activities as well as (7) IκB expression. However, administration of the PPAR-β/δ antagonist GSK0660 abolished these protective effects. These findings indicate that activation of PPAR-β/δ ameliorates hyperoxia-induced ALI in rats by up-regulating antioxidant enzyme activity as well as suppressing inflammation and apoptosis.
Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
Xiao-Chen
XC
Bao
Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China. Electronic address: zhouqybb@gmail.com.
Yi-Qun
YQ
Fang
Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
Pu
P
You
Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
Shi
S
Zhang
Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
Jun
J
Ma
D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000150:complications*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D047494:PPAR delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011312:Pressure; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D019141:Respiratory System Agents / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors; D010636:Phenols; D013438:Sulfhydryl Compounds
D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047494:PPAR delta; D048068:PPAR-beta; D019141:Respiratory System Agents; D013450:Sulfones; D013844:Thiazoles; D013876:Thiophenes; C529769:GSK0660; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds
Apoptosis; Inflammation; Peroxidase proliferator-activated receptor; Pulmonary oxygen toxicity