Abstract
The nuclear transcription factor, CCAAT/enhancer binding protein α (C/EBPα) is expressed at high levels in the liver and inhibits growth in cultured cells. We have tested the correlation between C/EBPα levels, cell cycle proteins and hepatocyte proliferation in old and young animals as an in vivo model system in which the proliferative response to partial hepatectomy (PH) has been shown to be reduced and delayed in old animals. Here we present evidence that the expression of C/EBPα in old rats (24 months) differs from its expression in young animals (6-10 months) during liver regeneration. Induction of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at 24 h after PH in young rats but is delayed and reduced in old animals. Induction of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver of old rats than in the liver of young animals, confirming the reduced proliferative response in old animals. In young rats, the normal regenerative response involves a reduction of 3-4-fold in the levels of C/EBPα protein at 3-24 h. In old animals, C/EBPα is not reduced within 24 h after PH, but a decrease of C/EBPα protein levels can be detected at 72 h after PH. Induction of C/EBPβ, another member of the C/EBP family, is delayed in old animals. Changes in the expression of C/EBP proteins are accompanied by alteration of the CDK inhibitor, p21, which is also decreased in young rats after PH, but in old animals remains unchanged. High levels of p21 protein in older animals correlate with the lack of cdk2 activation. We suggest that the failure to reduce the amount of C/EBPα and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3293-3299 |
| Number of pages | 7 |
| Journal | Nucleic Acids Research |
| Volume | 26 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 1 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
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Regenerating livers of old rats contain high levels of C/EBPα that correlate with altered expression of cell cycle associated proteins. / Timchenko, Nikolai A.; Wilde, Margaret; Kosai, Ken Lchiro; Heydari, Ahmed; Bilyeu, Timothy A.; Finegold, Milton J.; Mohamedali, Khalid; Richardson, Arlan; Darlington, Gretchen J.
In: Nucleic Acids Research, Vol. 26, No. 13, 01.07.1998, p. 3293-3299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regenerating livers of old rats contain high levels of C/EBPα that correlate with altered expression of cell cycle associated proteins
AU - Timchenko, Nikolai A.
AU - Wilde, Margaret
AU - Kosai, Ken Lchiro
AU - Heydari, Ahmed
AU - Bilyeu, Timothy A.
AU - Finegold, Milton J.
AU - Mohamedali, Khalid
AU - Richardson, Arlan
AU - Darlington, Gretchen J.
PY - 1998/7/1
Y1 - 1998/7/1
N2 - The nuclear transcription factor, CCAAT/enhancer binding protein α (C/EBPα) is expressed at high levels in the liver and inhibits growth in cultured cells. We have tested the correlation between C/EBPα levels, cell cycle proteins and hepatocyte proliferation in old and young animals as an in vivo model system in which the proliferative response to partial hepatectomy (PH) has been shown to be reduced and delayed in old animals. Here we present evidence that the expression of C/EBPα in old rats (24 months) differs from its expression in young animals (6-10 months) during liver regeneration. Induction of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at 24 h after PH in young rats but is delayed and reduced in old animals. Induction of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver of old rats than in the liver of young animals, confirming the reduced proliferative response in old animals. In young rats, the normal regenerative response involves a reduction of 3-4-fold in the levels of C/EBPα protein at 3-24 h. In old animals, C/EBPα is not reduced within 24 h after PH, but a decrease of C/EBPα protein levels can be detected at 72 h after PH. Induction of C/EBPβ, another member of the C/EBP family, is delayed in old animals. Changes in the expression of C/EBP proteins are accompanied by alteration of the CDK inhibitor, p21, which is also decreased in young rats after PH, but in old animals remains unchanged. High levels of p21 protein in older animals correlate with the lack of cdk2 activation. We suggest that the failure to reduce the amount of C/EBPα and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH.
AB - The nuclear transcription factor, CCAAT/enhancer binding protein α (C/EBPα) is expressed at high levels in the liver and inhibits growth in cultured cells. We have tested the correlation between C/EBPα levels, cell cycle proteins and hepatocyte proliferation in old and young animals as an in vivo model system in which the proliferative response to partial hepatectomy (PH) has been shown to be reduced and delayed in old animals. Here we present evidence that the expression of C/EBPα in old rats (24 months) differs from its expression in young animals (6-10 months) during liver regeneration. Induction of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at 24 h after PH in young rats but is delayed and reduced in old animals. Induction of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver of old rats than in the liver of young animals, confirming the reduced proliferative response in old animals. In young rats, the normal regenerative response involves a reduction of 3-4-fold in the levels of C/EBPα protein at 3-24 h. In old animals, C/EBPα is not reduced within 24 h after PH, but a decrease of C/EBPα protein levels can be detected at 72 h after PH. Induction of C/EBPβ, another member of the C/EBP family, is delayed in old animals. Changes in the expression of C/EBP proteins are accompanied by alteration of the CDK inhibitor, p21, which is also decreased in young rats after PH, but in old animals remains unchanged. High levels of p21 protein in older animals correlate with the lack of cdk2 activation. We suggest that the failure to reduce the amount of C/EBPα and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032125606&partnerID=8YFLogxK
U2 - 10.1093/nar/26.13.3293
DO - 10.1093/nar/26.13.3293
M3 - Article
C2 - 9628932
AN - SCOPUS:0032125606
VL - 26
SP - 3293
EP - 3299
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 13
ER -