Document Detail


Abnormal synthesis of cartilage-characteristic proteoglycan in azaserine-induced micromelial limbs.
MedLine Citation:
PMID:  2775238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Administration of azaserine (250 micrograms) to day-4 chick embryos in ovo was shown to induce micromelial limbs. In the present study, biosynthesis of cartilage-characteristic proteoglycan H (PG-H) as an index of limb chondrogenesis was examined in normal and micromelial hind limbs from day-7 chick embryos by biochemical and immunological methods. (1) Metabolic labelling of the micromelial limbs with [6-3H]-glucose and [35S]sulphate, followed by analysis of labelled proteoglycans by glycerol-density-gradient centrifugation under dissociative conditions, showed a marked reduction in PG-H synthesis. (2) PG-H synthesized by micromelial limbs differed from that synthesized by normal limbs in possessing a slower sedimenting velocity and much lower amounts of chondroitin sulphates. (3) The amount of PG-H core protein in micromelial limbs was significantly decreased to about 19% on a per limb basis and about 42% on a per DNA basis of that in normal limbs, as determined by e.l.i.s.a. (4) The transition from PG-M to PG-H during limb formation was retarded in micromelial limbs as judged by an indirect immunofluorescence technique using antibodies against PG-M and PG-H. (5) The deficiency of incorporation of labelled glucose into chondroitin sulphate chains of PG-H in micromelial limbs was partially restored by using [6-3H]-glucosamine as a precursor, suggesting that the synthesis of UDP-N-acetylhexosamine, required for chondroitin sulphate chain synthesis of PG-H in micromelial limbs, was decreased. These results suggest that the reduction in the synthesis of PG-H as well as the production of an abnormal form of PG-H during a critical period of limb morphogenesis may be important factors in explaining the micromelia induced by azaserine.
Authors:
A Honda; I Tsuboi; K Kimata; Y Hirabayashi; K Yamada; Y Mori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  261     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1989 Jul 
Date Detail:
Created Date:  1989-10-12     Completed Date:  1989-10-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  627-35     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / metabolism*
Animals
Azaserine / toxicity*
Cartilage / metabolism*
Chick Embryo
Hindlimb / abnormalities*,  drug effects,  metabolism
Proteoglycans / biosynthesis*
Chemical
Reg. No./Substance:
0/Proteoglycans; 115-02-6/Azaserine
Comments/Corrections

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