Cyclin D1 is up-regulated in hepatocytes in vivo following cell-cycle block induced by retrorsine.

Abstract:

BACKGROUND/AIMS:We reported massive liver repopulation by transplanted hepatocytes in rats given retrorsine (RS), a pyrrolizidine alkaloid which blocks proliferation of resident cells. In these studies, molecular alterations induced by RS on hepatocyte cell cycle were investigated. METHODS:Animals were treated according to the protocol for liver repopulation, i.e. two injections of RS (30 mg/kg) followed by two-thirds partial hepatectomy (PH) and were sacrificed at various time points thereafter. Livers were analyzed for the expression of cell cycle-related genes. RESULTS:Prior to PH, increased cyclin D1 mRNA and protein levels were found in livers of RS-treated rats. Expression of PCNA was also increased; however, DNA synthesis was not significantly changed. Other cyclins, including cyclin B and cyclin E, were not induced. Cyclin D1 expression increased in controls post-PH and then declined by 48 h, as expected. By contrast, no such modulation of cyclin D1 levels was seen in RS group receiving PH and expression remained high at 48 h, without mitotic division. CONCLUSIONS:Exposure to RS is able to block cell cycle progression after cyclin D1 and PCNA induction, but prior to S phase. Such persistent block outside the resting phase may contribute to the selective replacement of resident cells during liver repopulation.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Pitzalis S,Doratiotto S,Greco M,Montisci S,Pasciu D,Porcu G,Pani P,Laconi S,Laconi E

doi

10.1016/j.jhep.2005.03.029

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

485-90

issue

3

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(05)00313-2

journal_volume

43

pub_type

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