dl-propranolol negatively regulates the transcription of proliferating cell nuclear antigen (PCNA)-gene and thereby suppresses DNA synthesis in regenerating rat liver.
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, p21WAF1, and p27KIP1 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 43kDa 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.
Hong
J H
JH
College of Pharmacy, Seoul National University, Korea.
Hwang
E S
ES
Lee
C H
CH
Lee
Y H
YH
Lee
S K
SK
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
D017362:Cyclic AMP Response Element-Binding Protein; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D004247:DNA; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases