PMID- 17315247
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20131121
IS  - 1542-975X (Print)
IS  - 1542-975X (Linking)
VI  - 78
IP  - 4
DP  - 2006 Dec
TI  - Inhibition of histone deacetylase as a new mechanism of teratogenesis.
PG  - 345-53
AB  - Histone deacetylases (HDACs) are nuclear and cytoplasmic enzymes that deacetylate 
      a number of substrates, of which histones are the best known and described in the 
      literature. HDACs are present in eukaryotic and bacteria cells, and are 
      fundamental for a number of cellular functions, including correct gene 
      expression. Surprisingly, only up to 20% of the whole genome is controlled by 
      HDACs, but key processes for survival, proliferation, and differentiation have 
      been strictly linked to HDAC enzyme functioning. The use of HDAC inhibitors 
      (HDACi) has been proposed for the treatment of neoplastic diseases. Their 
      effectiveness has been suggested for a number of liquid and solid tumors, 
      particularly acute promyelocytic leukemia (APL). The role of HDACs in embryo 
      development is currently under investigation. Published data indicate knockout 
      phenotype analysis to be of particular interest, in which a number of HDACs play 
      a key role during development. Little data have been published on the effects of 
      HDACi on embryonic development, although for valproic acid (VPA), literature from 
      the 1980s described its teratogenic effects in experimental animals and humans. 
      To date, all tested HDACi have shown teratogenic effects similar to those 
      described for VPA when tested in zebrafish, Xenopus laevis, and mice. HDACs were 
      also able to alter embryo development in invertebrates and plants. A model, 
      similar to that proposed in APL, involving retinoic acid receptors (RAR) and 
      tissue specific Hox gene expression, is suggested to explain the HDAC effects on 
      embryo development.
CI  - Copyright (c) 2007 Wiley-Liss, Inc.
FAU - Menegola, Elena
AU  - Menegola E
AD  - Department of Biology, University of Milan, Milan, Italy. elena.menegola@unimi.it
FAU - Di Renzo, Francesca
AU  - Di Renzo F
FAU - Broccia, Maria Luisa
AU  - Broccia ML
FAU - Giavini, Erminio
AU  - Giavini E
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Birth Defects Res C Embryo Today
JT  - Birth defects research. Part C, Embryo today : reviews
JID - 101167665
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Abnormalities, Drug-Induced/*enzymology/*etiology
MH  - Animals
MH  - Embryonic Development/drug effects/genetics/physiology
MH  - Enzyme Inhibitors/therapeutic use/*toxicity
MH  - Female
MH  - Genes, Homeobox
MH  - *Histone Deacetylase Inhibitors
MH  - Humans
MH  - Models, Biological
MH  - Neoplasms/drug therapy
MH  - Pregnancy
MH  - Receptors, Retinoic Acid/metabolism
MH  - Teratogens/*toxicity
MH  - Tretinoin/metabolism
RF  - 108
EDAT- 2007/02/23 09:00
MHDA- 2007/04/25 09:00
CRDT- 2007/02/23 09:00
PHST- 2007/02/23 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2007/02/23 09:00 [entrez]
AID - 10.1002/bdrc.20082 [doi]
PST - ppublish
SO  - Birth Defects Res C Embryo Today. 2006 Dec;78(4):345-53. doi: 10.1002/bdrc.20082.