Molecular cloning and characterization of human cardiac α- and β-form myosin heavy chain complementary DNA clones: regulation of expression during development and pressure overload in human atrium

We have constructed and characterized two types of myosin heavy chain (MHC) cDNA clones (pHMHC2, pHMHC5) from a fetal human heart cDNA library. Comparison of the nucleotide and deduced amino acid sequences between pHMHC2 and pHMHC5 shows 95.1 and 96.2% homology, respectively. The carboxyl-terminal p...

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Bibliographic Details
Published in:The Journal of clinical investigation 1988-08, Vol.82 (2), p.524-531
Main Authors: KURABAYASHI, M, TSUCHIMOCHI, H, KOMURO, I, TAKAKU, F, YAZAKI, Y
Format: Article
Language:English
Subjects:
Adult
Aged
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Cardiomegaly - genetics
Cardiomegaly - metabolism
Cloning, Molecular
DNA - isolation & purification
Embryonic and Fetal Development
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Heart Atria - analysis
Heart Atria - growth & development
Heart Atria - metabolism
Humans
Isoenzymes - genetics
Isoenzymes - isolation & purification
Isoenzymes - metabolism
Male
Middle Aged
Molecular and cellular biology
Molecular Sequence Data
Myocardium - analysis
Myocardium - metabolism
Myosins - genetics
Myosins - isolation & purification
Myosins - metabolism
Rats
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Summary:We have constructed and characterized two types of myosin heavy chain (MHC) cDNA clones (pHMHC2, pHMHC5) from a fetal human heart cDNA library. Comparison of the nucleotide and deduced amino acid sequences between pHMHC2 and pHMHC5 shows 95.1 and 96.2% homology, respectively. The carboxyl-terminal peptide and 3'-untranslated (3'-UT) regions are highly divergent and specific for these cDNA clones. By using the synthetic oligonucleotide probes that are complementary to the unique 3'-UT regions of these cDNA clones, we demonstrate that pHMHC2 is exclusively transcribed in the atrium, whereas the mRNA for pHMHC5 is predominantly expressed in the ventricle. This result indicates that pHMHC2 and pHMHC5 code for alpha- and beta-form MHCs, respectively. Furthermore, we show that beta-form MHC mRNA is expressed in adult atrium at a low level but scarcely expressed in fetal atrium. Finally, we demonstrate that MHC isozymic transition in pressure-overloaded atrium is, at least in part, regulated at a pretranslational level.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci113627