Heat shock protein 27 protects lung epithelial cells from hyperoxia-induced apoptotic cell death.
Oxygen toxicity or hyperoxia is one of the major contributing factors in the development of bronchopulmonary dysplasia. Heat shock protein 27 (Hsp27) is an important chaperone protein in the postnatal lung development. However, the role of Hsp27 in lung epithelial cells during hyperoxia is unclear. Our studies by cDNA array and immunohistochemistry revealed that hyperoxia decreased Hsp27 expression in newborn rat lungs. Western blot showed that hyperoxic treatment significantly decreased Hsp27 protein expression in cultured human lung epithelial cells (A549). The expression of Hsp27 was decreased approximately twofold after 24-h and threefold after 48- and 72-h hyperoxic exposure compared with that of the A549 cells exposed to normoxia (p < 0.05, n = 3). Knockdown of Hsp27 expression by siRNA resulted in more apoptotic cell death in A549 cells. Overexpression of Hsp27 reduced hyperoxia-induced apoptotic cell death to 9.2% in Hsp27 overexpressing A549 cells from 12.6% in control A549 cells after 72-h hyperoxic exposure (p < 0.01, n = 8-9). Overexpression of Hsp27 also diminished hyperoxia-induced caspase-9 activation in A549 cells. Our results demonstrated that hyperoxia decreased Hsp27 expression in newborn rat lung and cultured human lung epithelial cells. Overexpression of Hsp27 could reduce hyperoxia-induced apoptosis in cultured human lung epithelial cells.
Shao
Lei
L
Department of Pathology, The Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City, Kansas City, Missouri 64108, USA.
Perez
Ricardo E
RE
Gerthoffer
William T
WT
Truog
William E
WE
Xu
Dong
D
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D013997:Time Factors
D055551:HSP27 Heat-Shock Proteins; D053453:Caspase 9