Document Detail


Induction of cell-cycle arrest by all-trans retinoic acid in mouse embryonic palatal mesenchymal (MEPM) cells.
MedLine Citation:
PMID:  15537748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
all-trans retinoic acid (atRA), the oxidative metabolite of vitamin A, is essential for normal embryonic development. Also, high levels of atRA are teratogenic in many species and can effectively induce cleft palate in the mouse. Most cleft palate resulted from the failed fusion of secondary palate shelves, and maintenance of the normal cell proliferation is important in this process of shelf growth. To clarify the mechanism by which atRA causes cleft palate, we investigated the effect of atRA on proliferation activity and cell cycle distribution in mouse embryonic palatal mesenchymal (MEPM) cells. atRA inhibited the growth of MEPM cells by inducing apoptosis in a dose-dependent manner. atRA also caused a G1 block in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase, as determined by flow cytometry. We next investigated the effects of atRA on molecules that regulate the G1 to S phase transition. These studies demonstrated that atRA inhibited expression of cyclins D and E at the protein level. Furthermore, atRA treatment reduced phosphorylated Rb and decreased cdk2 and cdk4 kinase activity. These data suggest that atRA had antiproliferative activity by modulating G1/S cell cycle regulators and by inhibition of Rb phosphorylation in MEPM cells, which might account for the pathogenesis of cleft palate induced by retinoic acid.
Authors:
Zengli Yu; Jiuxiang Lin; Ying Xiao; Jing Han; Xingzhong Zhang; Haichao Jia; Yunan Tang; Yong Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-10
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  83     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-05     Completed Date:  2005-05-05     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  349-54     Citation Subset:  IM    
Affiliation:
School of Stomatology, Peking University, Beijing, 100081, China; School of Public Health, Peking University, Beijing, 100083, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
CDC2-CDC28 Kinases / metabolism
Cell Cycle / drug effects*
Cell Survival / drug effects
Cells, Cultured
Cyclin D
Cyclin E / metabolism
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases / metabolism
Cyclins / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Flow Cytometry
Male
Mesoderm / drug effects*,  metabolism,  pathology
Mice
Mice, Inbred ICR
Palate / drug effects*,  embryology,  metabolism
Phosphorylation
Proto-Oncogene Proteins / metabolism
Retinoblastoma Protein / metabolism
Teratogens / toxicity*
Tretinoin / toxicity*
Chemical
Reg. No./Substance:
0/Cyclin D; 0/Cyclin E; 0/Cyclins; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Teratogens; 302-79-4/Tretinoin; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cdk2 protein, mouse; EC 2.7.11.22/Cdk4 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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