Document Detail

Effects of supplemental L-methionine on E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane]-induced dysmorphology in rat embryos cultured in vitro.
MedLine Citation:
PMID:  15041779     Owner:  NLM     Status:  MEDLINE    
E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane] is teratogenic, inducing a spec-trum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that E-64-induced malformations result from embryonic nutritionaldeficiency, without affecting the maternal nutritional status. This has provided a useful model with which to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects. In the current investigation, we examined effects of L-methionine on E-64-induced embryotoxicity in vitro. For these experiments, we cultured rat embryos 9.5 days postconception (p.c.) for 48 hours with E-64 and/or L-methionine. We found that the addition of L-methionine to E-64-exposed cultures reduced optic abnormality and increased embryo protein. These results suggest that embryopathy largely results from a deficiency of L-methionine although E-64 limits the supply of all amino acids to the embryo. Furthermore, although endocytosis and degradation of proteins by the visceral yolk sac (VYS) supply most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support those of previous investigations that suggest L-methionine is a limiting nutrient for embryonic development.
Kouichi Yoshidome; Hidehiko Kobae; Kimie Yamamoto; Kiyoko Sameshima; Koichiro Miyata; Yoshifumi Kawano
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Congenital anomalies     Volume:  43     ISSN:  0914-3505     ISO Abbreviation:  Congenit Anom (Kyoto)     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2004-03-25     Completed Date:  2004-06-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9306292     Medline TA:  Congenit Anom (Kyoto)     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  280-5     Citation Subset:  IM    
Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
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MeSH Terms
Abnormalities, Drug-Induced / prevention & control*
Culture Techniques
Embryonic and Fetal Development / drug effects*
Leucine / analogs & derivatives*,  toxicity*
Methionine / administration & dosage*,  pharmacology
Rats, Wistar
Teratogens / toxicity*
Reg. No./Substance:
0/Teratogens; 61-90-5/Leucine; 63-68-3/Methionine; 66701-25-5/E 64

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

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