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ARTICLES

Changes in mitochondrial DNA in cardiac hypertrophy in the rat.

C Rajamanickam, S Merten, B Kwiatkowska-Patzer, C H Chuang, R Zak, M Rabinowitz
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https://doi.org/10.1161/01.RES.45.4.505
Circulation Research. 1979;45:505-515
Originally published October 1, 1979
C Rajamanickam
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S Merten
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B Kwiatkowska-Patzer
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C H Chuang
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R Zak
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M Rabinowitz
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Abstract

We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of the mtDNA was assessed from its molecular conformation (open and closed circles) and by renaturation-kinetic analysis. The mtDNA concentration in mitochondria, expressed as micrograms of DNA per milligram of mitochondrial protein, increased 2, 4, and 7 days postoperatively by 21, 73, and 98%, respectively. Similar results were obtained when mtDNA was expressed per nonomole of cytochrome a. The population of replicative intermediates of mtDNA was analyzed by electron microscopy. In normal hearts, we observed molecular forms characteristic of animal mtDNA, such as circular monomers and dimers, catenated molecules, D-loops, expanded D-loops, and gapped molecules. D-loop frequency, which was near 50% in the mtDNA of control hearts, was markedly reduced to 5-7% in hypertrophying hearts. This result indicates that the increase in replicative flux of mtDNA is associated with the removal of a block in the conversion of D-loops to other intermediates.

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Circulation Research
October 1, 1979, Volume 45, Issue 4
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    Changes in mitochondrial DNA in cardiac hypertrophy in the rat.
    C Rajamanickam, S Merten, B Kwiatkowska-Patzer, C H Chuang, R Zak and M Rabinowitz
    Circulation Research. 1979;45:505-515, originally published October 1, 1979
    https://doi.org/10.1161/01.RES.45.4.505

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    Changes in mitochondrial DNA in cardiac hypertrophy in the rat.
    C Rajamanickam, S Merten, B Kwiatkowska-Patzer, C H Chuang, R Zak and M Rabinowitz
    Circulation Research. 1979;45:505-515, originally published October 1, 1979
    https://doi.org/10.1161/01.RES.45.4.505
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