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  • Title: Molecular basis of pathophysiology of Indian childhood cirrhosis: role of nuclear copper accumulation in liver.
    Author: Prasad R, Kaur G, Nath R, Walia BN.
    Journal: Mol Cell Biochem; 1996 Mar 09; 156(1):25-30. PubMed ID: 8709972.
    Abstract:
    Indian Childhood Cirrhosis (ICC) is a disease of abnormal copper metabolism commonly characterized by swelling and degeneration of liver cells along with the presence of orcein staining deposits of copper. Hepatic copper content of ICC patients was about 43 fold higher than those of control subjects. The data on sub-cellular distribution of copper revealed massive accumulation of Copper (73%) of total cell copper) in the nuclear fraction (455 micrograms Cu/g tissue nuclei). On further distribution of copper in nuclear fraction, the enrichment of copper in heterochromatin and euchromatin of ICC nuclei was found to be 48 and 15 fold higher over control fractions respectively. The ultra-violet spectra of heterochromatin and euchromatin isolated from ICC nuclear fraction showed a broad absorption maxima as compared to controls. Further, A260/A280 ratio was markedly lower in heterochromatin and euchromatin of ICC liver in comparison to controls. An antioxidant enzyme, catalase activity was also significantly reduced in ICC liver as compared to control. Further, DNA fragmentation studies indicated that there was significantly increased DNA fragmentation in ICC liver. Collectively, these findings suggest that massive accumulation of copper in nucleus and decrease in catalase activity was associated with DNA fragmentation in hepatocyte of ICC disease.
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