The ER stress pathway involving CHOP is activated in the lungs of LPS-treated mice.
CHOP is a C/EBP family transcription factor involved in endoplasmic reticulum (ER) stress-mediated apoptosis. To determine if the ER stress pathway is involved in the pathogenesis of LPS-treated mouse lung injury, mice were given lipopolysaccharide (LPS) intraperitoneally. The mRNAs for activating transcription factor (ATF) 4 and X-box binding protein (XBP) 1, transcriptional activators of the CHOP gene, and that for CHOP were induced by or after the LPS treatment. Apoptosis induced by LPS treatment was suppressed in the lungs of Chop-knockout mice. Overexpression of CHOP induced apoptosis in a lung cancer-derived cell line. These results suggest that the ER stress pathway, involving CHOP, is activated and plays a role in the pathogenesis of septic shock lung.
Endo
Motoyoshi
M
Departments of Molecular Genetics and Respiratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Oyadomari
Seiichi
S
Suga
Moritaka
M
Mori
Masataka
M
Gotoh
Tomomi
T
D051701:Activating Transcription Factor 4 / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000071717:X-Box Binding Protein 1
C081452:Atf4 protein, mouse; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP