Regulation of LPS-mediated induction of C/EBP delta gene expression in livers of young and aged mice.
The C/EBP family of transcription factors plays a major role in the regulation of families of stress response genes, in particular, the acute phase response genes. We have examined expression of the C/EBP delta gene during the bacterial lipopolysaccharide mediated induction of the acute phase response in livers of young (4 months) and aged (24-28 months) male C57B1/6 mice by Northern, Western, and Southwestern analyses. C/EBP delta mRNA is present at a low constitutive level, is induced by lipopolysaccharide, and reaches the same induced level in young and aged mice. Aged mice, however, show a higher constitutive, uninduced mRNA pool level and a delay in recovery to uninduced levels after lipopolysaccharide treatment. C/EBP delta mRNA is observable 30 min after lipopolysaccharide in total RNA, cytoplasmic and polysomal fractions. Specific full length 28-kDa nascent peptides are detectable in polysomes 90 min after lipopolysaccharide. mRNA and nascent peptides cosediment with large polysomes and C/EBP delta mRNA is shifted to larger polysomes in lipopolysaccharide treated aged mice, consistent with an increased rate of initiation. Specific DNA-binding activity of C/EBP delta protein in nuclear extracts was examined by electromobility shift and antibody supershift assay. The levels of C/EBP delta binding-activity, are consistent with the changes in mRNA levels in young lipopolysaccharide treated livers. These studies support our hypothesis that aged mice exhibit a state of chronic inflammation or stress in the absence of a stressor.
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0643, USA.
J P
JP
Rabek
S
S
Scott
C C
CC
Hsieh
P D
PD
Reisner
J
J
Papaconstantinou
D000210:Acute-Phase Reaction / Q000235:genetics; D000375:Aging / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000187:drug effects* / Q000235:genetics*; D010455:Peptides / Q000032:analysis / Q000235:genetics; D011132:Polyribosomes / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D010455:Peptides; D012333:RNA, Messenger