Alterations in mitochondrial DNA and enzyme activities in hypertrophied myocardium of stroke-prone SHRS.
To clarify the pathophysiological alteration of mitochondria in SHRSP hypertrophied heart, mitochondria-related enzyme changes were examined and compared to those in WKY. Furthermore, the structure alteration in mitochondrial DNA (mtDNA) was examined by restriction fragment length polymorphisms (RFLPs). Both isocitrate dehydrogenase (ICDH) and cytochrome c oxidase (COX), which are related to energy production or the respiratory chain in mitochondria, were significantly lower in SHRSP myocardium than in WKY. Furthermore, superoxide dismutase (SOD), a potent radical scavenger, was also lower in SHRSP myocardium. RFLPs analysis by Rsa I revealed two deletions in the electrophoretic band in the SHRSP myocardium, but not in the liver. These findings suggest that mitochondrial dysfunction, especially lower energy production, could be an important factor for the pathogenesis of further myocardial degeneration. The results also suggest that mitochondrial alterations, in the membrane system as well as mtDNA, may be caused by oxidative stress in mitochondria because of decreased scavenging activity.
Tokoro
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T
First Department of Pathology, Kinki University School of Medicine, Osaka, Japan.
Ito
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Suzuki
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T
D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D004272:DNA, Mitochondrial; D007521:Isocitrate Dehydrogenase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV