Geranylgeranylacetone ameliorates lung ischemia/reperfusion injury by HSP70 and thioredoxin redox system: NF-kB pathway involved.
Geranylgeranylacetone (GGA) has been clinically used as an anti-ulcer drug. In the present study, we explored the protective effects of GGA on lung ischemia/reperfusion injury (IRI) and the underlying mechanism. The results demonstrated that GGA ameliorated the lung biochemical and histological alterations induced by IRI, which was reversed by HSP70 inhibition. To further explore the mechanism of GGA action, we focused on NF-kB and thioredoxin (Trx) redox system. It was shown that GGA induced the HSP70 and Trx-1 expression, NF-kB nuclear translocation and activated thioredoxin reductase (TrxR). The Trx-1 expression and TrxR activity was suppressed by HSP70 and NF-kB inhibition, while the nuclear NF-kB p65 expression was suppressed by HSP70 inhibitor. These results indicated that GGA may protect rat lung against IRI by HSP70 and Trx redox system, in which NF-kB pathway may be involved.
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: weijuncaotongji@sina.com.
Weijun
W
Cao
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Manhui
M
Li
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Jianxiong
J
Li
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Chengwei
C
Li
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Xin
X
Xu
Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Weiqing
W
Gu
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013879:Thioredoxins / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D013879:Thioredoxins; C031049:geranylgeranylacetone
Geranylgeranylacetone; HSP70; Lung ischemia-reperfusion injury; NF-kB; Thioredoxin