Adenosine Administration Accelerates Progression of the Cell Cycle during Rat Liver Regeneration Induced by One-Third Hepatectomy
We have shown that adenosine administration is capable of reversing fibrosis in the carbon tetrachloride-induced rat cirrhotic liver, stimulating the diminished proliferative potential of the cirrhotic liver. To characterize adenosine actions on liver cellular proliferation, we used rats subjected t...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 331; no. 1; pp. 122 - 132 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.10.2009
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Subjects | |
Online Access | Get full text |
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Summary: | We have shown that adenosine administration is capable of reversing fibrosis in the carbon tetrachloride-induced rat cirrhotic
liver, stimulating the diminished proliferative potential of the cirrhotic liver. To characterize adenosine actions on liver
cellular proliferation, we used rats subjected to one-third partial hepatectomy (PH). In PH animals acutely administered with
adenosine (25â200 mg/kg b.w.), parameters indicative of cell proliferation were determined. In addition, hepatocyte growth
factor (HGF), epidermal growth factor, and transforming growth factor-α, cyclins, members of the E2F family, proto-oncogenes,
and adenosine-receptors were determined through Western blot analyses. Adenosine (100 mg/kg body weight) induced an earlier
increase in liver cell proliferation as evidenced by enhanced levels of proliferating cell nuclear antigen, nuclear Ki-67
antigen, and those for cyclins (D1, E, A, and B1), as well as by an increased mitotic index. These effects were also accompanied
for a long-lasting increase of serum and liver levels of HGF and liver expression of c-Met and HGF liver activator. Adenosine
effects on cell proliferation could be mediated by an early increase in E2F-1 and by that of c-Myc, despite the fact that
phosphorylation of the Rb protein and expression of E2F-3 were decreased. Moreover, the liver amount of specific receptors
for adenosine was not significantly changed by PH and/or adenosine treatment. In conclusion, these data suggest that adenosine
actions can accelerate and increase proliferation in a âprimedâ liver, mainly through enhancing c-Myc, E2F family, cell-cycle
cyclins, and HGF expression. Therefore, these pharmacological adenosine effects suggest a modulating role for the nucleoside
on mitogenic events once the liver has been triggered to proliferate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.109.156620 |