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Zinc-binding protein in the livers of neonatal, normal and partially hepatectomized rats.

ABSTRACT: In the livers of rats after partial hepatectomy the zinc concentration began to increase soon after the operation, reached a maximum value at 14h, and decreased to the original value by 25h after the operation. In contrast, the plasma zinc concentration continued to decrease during the first 10h after the operation and remained depressed for at least 28h. The plasma and hepatic zinc concentrations were relatively unaffected by sham-operation. Synchronous with the increase in the hepatic zinc concentration after the partial hepatectomy, there was an appearance of zinc-binding protein (Zn-binding protein) in the liver cytosol. Studies with small doses of actinomycin D and cycloheximide suggest that both RNA and protein syntheses are necessary for the induction of Zn-binding protein after partial hepatectomy. A high content of the Zn-binding protein was found in neonatal rat liver. The Zn-binding protein, however, was undetectable 40 days after birth. The Zn-binding protein was also found in the adult rat liver when stimulated to proliferate after the administration of isoprenaline followed by glucagon. These findings indicate a close linkage between the appearance of Zn-binding protein in the liver cytosol and the regulation of DNA synthesis.

SUBMITTER: Ohtake H

PROVIDER: S-EPMC1186005 | biostudies-other | 1978 Sep

REPOSITORIES: biostudies-other

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Project description:Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MV) derived from human liver stem cells (HLSC) were able to stimulate in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MV in the hepatocytes by an alpha4 integrin-dependent mechanism. However, when treated with RNase, MV despites their internalization were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MV were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MV were found to accelerate the morphological and functional recovery of liver in a model of 70% hepatectomy in rats by inducing an hepatocytes proliferation that was abolished by RNase treatment. Using human AGO2 gene, which is shuttled by MV, as a reporter gene, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MV. This suggest a translation of the MV shuttled mRNA within hepatocytes of treated rats. Conclusion: these results suggest that MV derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets. MV contained mRNA was submitted to microarray analysis not to define the amount of mRNA but only to define which transcripts were present. Total RNA was prepared from two independent preparation of vesicles. 250, 500 and 1000 ngs from each preparation were transformed in biotin-labeled cRNA. A simple statistical linear model was used to identify transcript signals linearly correlated to the increment of total RNA concentration used to prepare cRNA.

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Zinc-binding protein in the livers of neonatal, normal and partially hepatectomized rats.

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