PMID- 21415591 OWN - NLM STAT- MEDLINE DCOM- 20111026 LR - 20211109 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 43 IP - 4 DP - 2011 Apr 30 TI - Cathepsin B is activated as an executive protease in fetal rat alveolar type II cells exposed to hyperoxia. PG - 223-9 AB - Alveolar type II cells are main target of hyperoxia-induced lung injury. The authors investigated whether lysosomal protease, cathepsin B (CB), is activated in fetal alveolar type II cells in the transitional period from the canalicular to saccular stages during 65%-hyperoxia and whether CB is related to fetal alveolar type II cell (FATIIC) death secondary to hyperoxia. FATIICs were isolated from embryonic day 19 rats and exposed to 65%-oxygen for 24 h and 36 h. The cells exposed to room air were used as controls. Cell cytotoxicity was assessed by lactate dehydrogenase-release and flow cytometry, and apoptosis was analyzed by TUNEL assay and flow cytometry. CB activity was assessed by colorimetric assay, qRT-PCR and western blots. 65%-hyperoxia induced FATIIC death via necrosis and apoptosis. Interestingly, caspase-3 activities were not enhanced in FATIICs during 65%-hyperoxia, whereas CB activities were greatly increased during 65%-hyperoxia in a time-dependent manner, and similar findings were observed with qRT-PCR and western blots. In addition, the preincubation of CB inhibitor prior to 65%-hyperoxia reduced FATIIC death significantly. Our studies suggest that CB activation secondary to hyperoxia might have a relevant role in executing the cell death program in FATIICs during the acute stage of 65%-hyperoxia. FAU - Lee, Hyeon-Soo AU - Lee HS AD - Department of Pediatrics, Kangwon National University Hospital, Kangwon Naitonal University School of Medicine, Chuncheon, Korea. premee@kangwon.ac.kr FAU - Kim, Chun-Ki AU - Kim CK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.1 (Cathepsin B) RN - EC 3.4.22.1 (Ctsb protein, rat) RN - S88TT14065 (Oxygen) SB - IM MH - Alveolar Epithelial Cells/cytology/*metabolism MH - Animals MH - Caspase 3 MH - Cathepsin B/*metabolism MH - Cell Death MH - Cell Hypoxia MH - Enzyme Activation MH - Female MH - In Situ Nick-End Labeling MH - L-Lactate Dehydrogenase/analysis MH - Lung/metabolism MH - Necrosis/metabolism MH - Oxygen MH - Polymerase Chain Reaction MH - Pregnancy MH - Pulmonary Alveoli/cytology/embryology/*enzymology MH - Rats MH - Rats, Sprague-Dawley PMC - PMC3085741 EDAT- 2011/03/19 06:00 MHDA- 2011/10/27 06:00 PMCR- 2011/04/30 CRDT- 2011/03/19 06:00 PHST- 2011/03/19 06:00 [entrez] PHST- 2011/03/19 06:00 [pubmed] PHST- 2011/10/27 06:00 [medline] PHST- 2011/04/30 00:00 [pmc-release] AID - emm.2010.43.027 [pii] AID - 10.3858/emm.2011.43.4.027 [doi] PST - ppublish SO - Exp Mol Med. 2011 Apr 30;43(4):223-9. doi: 10.3858/emm.2011.43.4.027.