dl-Propranolol negatively regulates the transcription of proliferating cell nuclear antigen (PCNA)-gene and thereby suppresses DNA synthesis in regenerating rat liver

Jeong Ho Hong, Eun Sook Hwang, Chang Ho Lee, Yong Hee Lee, Seung Ki Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Previous reports have suggested that dl-propranolol (PRL) suppresses DNA synthesis by blocking cAMP-mediated signaling in rat liver after partial hepatectomy (PH). Here, we examined if PRL negatively regulates the expression of genes involved in cell cycle progression. Immunoblotting assays showed that the protein levels of cyclins A and E, Cdk2, p21(WAF1), and p27(KIP1) did not significantly change in liver tissues from either vehicle- or PRL-injected rats after PH. However, the levels of PCNA and PCNA-mRNA markedly decreased in the remnant liver in response to PRL-injection. Similarly, PCNA-CRE binding activity of nuclear 43 kDa CREB was suppressed, although the protein levels were not altered. We suggest that PRL negatively regulates the PCNA-gene transcription by interfering with the cAMP/PKA-mediated induction of CREB binding to the CRE-sequences and thereby suppresses DNA synthesis in regenerating rat liver.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalBiochemistry and Molecular Biology International
Volume42
Issue number1
DOIs
Publication statusPublished - 1997 Jun
Externally publishedYes

Keywords

  • CREB
  • PCNA
  • Regenerating rat liver
  • cAMP
  • dl-Propranolol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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