Document Detail


Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent.
MedLine Citation:
PMID:  8756678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human diploid fibroblasts (HDF) complete a limited number of cell divisions before entering a growth arrest state that is termed replicative senescence. Two histone deacetylase inhibitors, sodium butyrate and trichostatin A, dramatically reduce the HDF proliferative life span in a manner that is dependent on one or more cell doublings in the presence of these agents. Cells arrested and subsequently released from histone deacetylase inhibitors display markers of senescence and exhibit a persistent G1 block but remain competent to initiate a round of DNA synthesis in response to simian virus 40 T antigen. Average telomere length in prematurely arrested cells is greater than in senescent cells, reflecting a lower number of population doublings completed by the former. Taken together, these results support the view that one component of HDF senescence mimics a cell cycle-dependent drift in differentiation state and that propagation of HDF in histone deacetylase inhibitors accentuates this component.
Authors:
V V Ogryzko; T H Hirai; V R Russanova; D A Barbie; B H Howard
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  16     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-09-26     Completed Date:  1996-09-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5210-8     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2753, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Viral, Tumor / genetics,  physiology
Butyric Acid
Butyric Acids / pharmacology*
Cell Aging / drug effects*,  physiology
Cell Cycle / physiology*
Cell Division
Cell Line
Enzyme Inhibitors / pharmacology*
Fibroblasts / chemistry,  cytology,  drug effects*
Hela Cells / drug effects
Histone Deacetylase Inhibitors*
Histone Deacetylases / physiology
Humans
Hydroxamic Acids / pharmacology*
Retinoblastoma Protein / physiology
Telomere / ultrastructure
Transfection
Chemical
Reg. No./Substance:
0/Antigens, Viral, Tumor; 0/Butyric Acids; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Retinoblastoma Protein; 107-92-6/Butyric Acid; 58880-19-6/trichostatin A; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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


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