PMID- 20864682
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 177
IP  - 5
DP  - 2010 Nov
TI  - Hepatocyte proliferation during liver regeneration is impaired in mice with 
      methionine diet-induced hyperhomocysteinemia.
PG  - 2357-65
LID - 10.2353/ajpath.2010.091131 [doi]
AB  - Elevated homocysteine levels are defined as hyperhomocysteinemia (HHcy), a 
      disorder that is associated with cardiovascular and neurodegenerative diseases as 
      well as with hepatic fibrosis. Recent studies have shown that HHcy promotes 
      hepatic injury by increasing oxidative stress. Although homocysteine induces cell 
      cycle arrest in a variety of different cell types, it is not known whether HHcy 
      has a definitive role in hepatocyte proliferation during liver regeneration. In 
      this report, we investigated the effect of homocysteine on liver regeneration. 
      Our results demonstrated that mice with HHcy exhibited an impairment in liver 
      regeneration after partial hepatectomy, as measured by immunohistochemical 
      staining of proliferation cell nuclear antigen and bromodeoxyuridine 
      incorporation. Impaired proliferation was also correlated with reduced cyclin D1 
      induction and elevated expression levels of both p53 and p21Cip1. In addition, 
      the phosphorylation of Akt, which plays an essential role in normal regeneration 
      responses, was attenuated during the early phases of liver regeneration in HHcy 
      mice. Our results also indicated that the cAMP/protein kinase A pathway mediated 
      the inhibitory effect of homocysteine on liver regeneration. These findings 
      provide evidence that impairment of liver regeneration by HHcy may result in 
      delayed recovery from liver injury induced by homocysteine itself.
FAU - Liu, Wei-Hua
AU  - Liu WH
AD  - Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, 
      and the Department of General Surgery, The First People's Hospital of Kunming, 
      Kunming, Yunnan 650091, China.
FAU - Zhao, Yue-Shui
AU  - Zhao YS
FAU - Gao, Shun-Yu
AU  - Gao SY
FAU - Li, Shu-De
AU  - Li SD
FAU - Cao, Jun
AU  - Cao J
FAU - Zhang, Ke-Qin
AU  - Zhang KQ
FAU - Zou, Cheng-Gang
AU  - Zou CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100923
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 136601-57-5 (Cyclin D1)
RN  - AE28F7PNPL (Methionine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclin D1/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - *Diet
MH  - Hepatectomy
MH  - Hepatocytes/cytology/*physiology
MH  - Humans
MH  - Hyperhomocysteinemia/etiology/*physiopathology
MH  - Liver/pathology/physiology
MH  - Liver Regeneration/*physiology
MH  - Methionine/*administration & dosage/adverse effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC2966794
EDAT- 2010/09/25 06:00
MHDA- 2011/03/22 06:00
PMCR- 2011/11/01
CRDT- 2010/09/25 06:00
PHST- 2010/09/25 06:00 [entrez]
PHST- 2010/09/25 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - S0002-9440(10)60288-X [pii]
AID - 10.2353/ajpath.2010.091131 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 Nov;177(5):2357-65. doi: 10.2353/ajpath.2010.091131. Epub 2010 
      Sep 23.