Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein α and CCAAT/enhancer binding protein β isoform synthesis in control and LPS-treated livers

Ching Chyuan Hsieh, Wei Xiong, Qizhi Xie, Jeffrey P. Rabek, Sheen G. Scott, Mi Ra An, Peter D. Reisner, David T. Kuninger, John Papaconstantinou

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Abstract

The CCAAT/enhancer binding protein α (C/EBPα) and CCAAT/enhancer binding protein β (C/EBPβ) mRNAs are templates for the differential translation of several isoforms. Immunoblotting detects C/EBPαs with molecular masses of 42, 38, 30, and 20 kDa and C/EBPβs of 35, 20, and ~8.5 kDa. The DNA-binding activities and pool levels of p42(C/EBPα) and p30(C/EBPα) in control nuclear extracts decrease significantly whereas the binding activity and protein levels of the 20-kDa isoforms increase dramatically with LPS treatment. Our studies suggest that the LPS response involves alternative translational initiation at specific in-frame AUGs, producing specific C/EBPα and C/EBPβ isoform patterns. We propose that alternative translational initiation occurs by a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal aged mouse livers have decreased p42(C/EBPα) levels and binding activity, whereas those of p20(C/EBPα) and p20(C/ESPβ) are increased. However, translation of 42-kDa C/EBPα is not down-regulated on polysomes, suggesting that aging may affect its nuclear translocation. Furthermore, recovery of the C/EBPα- and C/EBPβ- binding activities and pool levels from an LPS challenge is delayed significantly in aged mouse livers. Thus, aged livers have altered steady- state levels of C/EBPα and C/EBPβ isoforms. This result suggests that normal aging liver exhibits characteristics of chronic stress and a severe inability to recover from an inflammatory challenge.

Original languageEnglish (US)
Pages (from-to)1479-1494
Number of pages16
JournalMolecular Biology of the Cell
Volume9
Issue number6
StatePublished - Jun 1998

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CCAAT-Enhancer-Binding Proteins
Protein Isoforms
Liver
Protein Binding
Polyribosomes
Protein C
Immunoblotting

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein α and CCAAT/enhancer binding protein β isoform synthesis in control and LPS-treated livers. / Hsieh, Ching Chyuan; Xiong, Wei; Xie, Qizhi; Rabek, Jeffrey P.; Scott, Sheen G.; An, Mi Ra; Reisner, Peter D.; Kuninger, David T.; Papaconstantinou, John.

In: Molecular Biology of the Cell, Vol. 9, No. 6, 06.1998, p. 1479-1494.

Research output: Contribution to journalArticle

Hsieh, Ching Chyuan ; Xiong, Wei ; Xie, Qizhi ; Rabek, Jeffrey P. ; Scott, Sheen G. ; An, Mi Ra ; Reisner, Peter D. ; Kuninger, David T. ; Papaconstantinou, John. / Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein α and CCAAT/enhancer binding protein β isoform synthesis in control and LPS-treated livers. In: Molecular Biology of the Cell. 1998 ; Vol. 9, No. 6. pp. 1479-1494.
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abstract = "The CCAAT/enhancer binding protein α (C/EBPα) and CCAAT/enhancer binding protein β (C/EBPβ) mRNAs are templates for the differential translation of several isoforms. Immunoblotting detects C/EBPαs with molecular masses of 42, 38, 30, and 20 kDa and C/EBPβs of 35, 20, and ~8.5 kDa. The DNA-binding activities and pool levels of p42(C/EBPα) and p30(C/EBPα) in control nuclear extracts decrease significantly whereas the binding activity and protein levels of the 20-kDa isoforms increase dramatically with LPS treatment. Our studies suggest that the LPS response involves alternative translational initiation at specific in-frame AUGs, producing specific C/EBPα and C/EBPβ isoform patterns. We propose that alternative translational initiation occurs by a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal aged mouse livers have decreased p42(C/EBPα) levels and binding activity, whereas those of p20(C/EBPα) and p20(C/ESPβ) are increased. However, translation of 42-kDa C/EBPα is not down-regulated on polysomes, suggesting that aging may affect its nuclear translocation. Furthermore, recovery of the C/EBPα- and C/EBPβ- binding activities and pool levels from an LPS challenge is delayed significantly in aged mouse livers. Thus, aged livers have altered steady- state levels of C/EBPα and C/EBPβ isoforms. This result suggests that normal aging liver exhibits characteristics of chronic stress and a severe inability to recover from an inflammatory challenge.",
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