PMID- 19460723 OWN - NLM STAT- MEDLINE DCOM- 20100504 LR - 20161125 IS - 1673-4254 (Print) IS - 1673-4254 (Linking) VI - 29 IP - 5 DP - 2009 May TI - [Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats]. PG - 970-3, 978 AB - OBJECTIVE: To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism. METHODS: Thirty SD rats were randomly divided into 3 groups, namely the normoxic group, hyperoxic group, and hyperoxic with MG-132 treatment group, and rat models of hyperoxic exposure-induced lung injury were established in the latter two groups. After pathological grading of the lung injury under optical microscope and determination of the wet/dry weight ratio of the lung tissue, the expressions of ubiquitin protein and nuclear factor-kappaB (NF-kappaB) p56 and the activity of proteasome 20S and myeloperoxidase (MPO) were detected. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions in the lung tissue were also detected. RESULTS: The rats with hyperoxic exposure showed obvious pulmonary edema and increased wet/dry weight ratio of the lung tissue (P<0.01), which were significantly alleviated with MG-132 treatment (P<0.01). Compared with the normoxic group, hyperoxic exposure resulted in significant lung pathologies (P<0.01), which was reduced after MG-132 treatment. Immunohistochemistry and Western blotting demonstrated increased expression of ubiquitin protein in the lung tissue after hyperoxic exposure (P<0.01), which was lowered by MG-132 treatment (P<0.01). Proteasome 20S activity was obviously enhanced in the hyperoxic group (P<0.01) but lowered by MG-132 treatment (P<0.01). Hyperoxic exposure also caused obviously enhanced MPO activity and expressions of NF-kappaB, TNF-alpha, and IL-6 (P<0.01), which were all reduced by MG-132 treatment (P<0.05). CONCLUSION: MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways. FAU - Huang, Yu-ge AU - Huang YG AD - Graduate College of Southern Medical Unversity, Guangzhou 510515, China. kenbobozj@yahoo.com.cn FAU - Feng, Zhi-chun AU - Feng ZC FAU - Yu, Yan-liang AU - Yu YL FAU - Xiao, Fang-fang AU - Xiao FF LA - chi PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Nan Fang Yi Ke Da Xue Xue Bao JT - Nan fang yi ke da xue xue bao = Journal of Southern Medical University JID - 101266132 RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Interleukin-6) RN - 0 (Leupeptins) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Ubiquitin) RN - EC 1.11.1.7 (Peroxidase) RN - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde) SB - IM MH - Animals MH - Animals, Newborn MH - Cysteine Proteinase Inhibitors/*pharmacology MH - Female MH - Hyperoxia/*complications MH - Interleukin-6/metabolism MH - Leupeptins/*pharmacology MH - Lung Injury/etiology/metabolism/*pathology MH - Male MH - NF-kappa B/*metabolism MH - Peroxidase/metabolism MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Tumor Necrosis Factor-alpha/metabolism MH - Ubiquitin/metabolism EDAT- 2009/05/23 09:00 MHDA- 2010/05/05 06:00 CRDT- 2009/05/23 09:00 PHST- 2009/05/23 09:00 [entrez] PHST- 2009/05/23 09:00 [pubmed] PHST- 2010/05/05 06:00 [medline] PST - ppublish SO - Nan Fang Yi Ke Da Xue Xue Bao. 2009 May;29(5):970-3, 978.