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Characterization of isolated mitochondria from heterozygous manganese superoxide dismutase knockout mice
Bibliografi
Author:
Williams, Melissa Dawn
;
Richardson, Arlan
(Advisor)
Topik:
BIOLOGY
;
ANIMAL PHYSIOLOGY|CHEMISTRY
;
BIOCHEMISTRY|BIOLOGY
;
MOLECULAR
Bahasa:
(EN )
ISBN:
0-591-89572-2
Penerbit:
THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO
Tahun Terbit:
1998
Jenis:
Theses - Dissertation
Fulltext:
9836049.pdf
(0.0B;
1 download
)
Abstract
This study compares oxidative damage and function in mitochondria isolated from the hearts and livers of the $Sod2/sp[-/+]$ and $Sod2/sp[+/+]$ mice. A 50% reduction in MnSOD activity was observed in the heart and liver mitochondria isolated from the $Sod2/sp[-/+]$ mice compared to the $Sod2/sp[+/+]$ mice. No change was observed in the activities of either Cu/ZnSOD or glutathione peroxidase in the mitochondria. A 30% decrease in total glutathione was observed in liver mitochondria from the $Sod2/sp[-/+]$ mice; however, the levels of total glutathione were similar in heart mitochondria from the $Sod2/sp[-/+]$ and $Sod2/sp[+/+]$ mice. The 50% reduction in MnSOD activity was associated with increased oxidative damage in mitochondrial protein in both liver and heart from the $Sod2/sp[-/+]$ mice, e.g., decreased activities of Fe-S proteins sensitive to oxidative stress (aconitase and NADH-oxidoreductase) and increased levels of carbonyl groups in mitochondrial proteins. An increase in the oxidation (8-hydroxydeoxyguanosine), in mtDNA was also observed in liver. However, there was no significant change in oxidative damage in the cytosolic proteins for heart or liver of the $Sod2/sp[-/+]$ or $Sod2/sp[+/+]$ mice. Also, there was no change in the oxidation of nuclear DNA from the livers of the $Sod2/sp[-/+]$ or $Sod2/sp[+/+]$ mice. The increase in oxidative damage in the $Sod2/sp[-/+]$ mice was correlated to alterations in mitochondrial function. Heart and liver mitochondria from the $Sod2/sp[-/+]$ mice showed decreased function of complex I of the mitochondrial respiratory chain. A significant decrease (30% to 35%) in the respiratory control ratio (RCR) was observed using the substrate glutamate/malate in mitochondria isolated from both the liver and heart of $Sod2/sp[-/+]$ mice. A decrease in RCR was also observed for substrates metabolized by complex II and complex III in both heart and liver mitochondria; however, this decrease was only significant in mitochondria from the liver. In addition, mitochondria isolated from heart and liver of the $Sod2/sp[-/+]$ mice showed an increase in the rate of induction of the permeability transition. In summary, mitochondria isolated from the hearts and livers of the $Sod2/sp[-/+]$ mice showed a gradual accumulation of oxidative damage, which was associated with changes in mitochondrial function.
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