Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells.
Expression of heat shock proteins (HSPs) is classically activated at temperatures above the physiologic range (>or=42 degrees C) via activation of the stress-activated transcription factor, heat shock factor-1 (HSF-1). Several studies suggest that less extreme hyperthermia, especially within the febrile range, as occurs during fever and exertional/environmental hyperthemia, can also activate HSF-1 and enhance HSP expression. We compared HSP72 protein and mRNA expression in human A549 lung epithelial cells continuously exposed to 38.5 degrees C, 39.5 degrees C, or 41 degrees C or exposed to a classic heat shock (42 degrees C for 2 h). We found that expression of HSP72 protein and mRNA increased linearly as incubation temperature was increased from 37 degrees C to 41 degrees C, but increased abruptly when the incubation temperature was raised to 42 degrees C. A similar response in luciferase activity was observed using A549 cells stably transfected with an HSF-1-responsive luciferase reporter plasmid. However, activation of intranuclear HSF-1 DNA-binding activity was comparable at 38.5 degrees C, 39.5 degrees C, and 41 degrees C and only modestly greater at 42 degrees C but the mobility of HSF1 protein on a denaturing gel was altered with increasing exposure temperature and was distinctly different at 42 degrees C. These findings indicate that the proportional changes in HSF-1-dependent HSP72 expression at febrile-range temperatures are dependent upon exposure time and temperature but not on the degree of HSF-1 DNA-binding activity. Instead, HSF-1-mediated HSP expression following hyperthermia and heat shock appears to be mediated, in addition to HSF-1 activation, by posttranslational modifications of HSF-1 protein.
Tulapurkar
Mohan E
ME
Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Asiegbu
Benedict E
BE
Singh
Ishwar S
IS
Hasday
Jeffrey D
JD
D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA