Ethanol reduces p38 kinase activation and cyclin D1 protein expression after partial hepatectomy in rats.
OBJECTIVE
Chronic ethanol consumption inhibits liver regeneration. We examined the effects of chronic ethanol consumption on two mitogen-activated protein kinases in relation to induction of cell cycle proteins after partial hepatectomy (PH).


METHODS
Male Wistar rats were ethanol-fed (EF) or pair-fed (PF) for 16 weeks before PH. Hepatic activation of extracellular signal regulated kinase (ERK)1/2, p38 kinase and expression of cyclinD1, cyclin-dependent kinase-4 (cdk4) and proliferating cell nuclear antigen (PCNA) were studied.


RESULTS
In PF rats, PH-induced p38 activation was evident at 2h and was maximal at 12h. There was a close temporal relationship between p38 activation, cyclin D1 and PCNA expression. Alcohol exposure reduced p38 activation, cyclin D1 and PCNA, each by approximately 50%. ERK1/2 activation occurred during the first 2h post-PH in both EF and PF rats, and there was no later increase in PF rats. In vivo inhibition of p38 suppressed PCNA expression whereas the effect of ERK1/2 inhibition was inconsistent.


CONCLUSIONS
p38 kinase activation is linked temporally with cyclin D1 expression after PH and appears to exert cell cycle control in the adult liver. p38 signaling also appears to be a target for the inhibitory effect of chronic alcohol on liver regeneration.
Hsu
Michael K H
MK
Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Westmead, NSW 2145, Australia.
Qiao
Liang
L
Ho
Vikki
V
Zhang
Bao-Hong
BH
Zhang
Hongxia
H
Teoh
Narci
N
Dent
Paul
P
Farrell
Geoffrey C
GC
D000437:Alcoholism / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019938:Cyclin D1; D000431:Ethanol; D051358:Cyclin-Dependent Kinase 4; D048051:p38 Mitogen-Activated Protein Kinases