Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments performed in different models of hepatic regeneration at the time of maximal DNA synthesis, determined by thymidine kinase activity assay, demonstrated that spermidine N8-acetyltransferase activity increased 48 hr after CCl4 administration (2-fold), 72 hr after CCl4 plus phenobarbital (3-fold) and 24 hr after partial hepatectomy (4.5-fold). On the contrary, at these times histone acetyltransferase activity diminished (approximately twofold) and was unchanged compared with control values in the liver of hepatotoxin-treated and hepatectomized rats, respectively. Histone acetylation was, however, enhanced 1.5-fold before the onset of DNA replication (14 hr), and 3.4-fold after the peak of DNA synthesis (32 hr) in the liver of hepatectomized rats. alpha-Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase that was administered to hepatectomized rats, blocked polyamine synthesis, thymidine kinase activity and consequently liver regeneration 24 hr after the surgery. In those conditions, spermidine N8-acetyltransferase activity was decreased approximately twofold, whereas histone acetyltransferase activity was elevated approximately twofold. All these effects were reversed by putrescine coadministration. Altogether, these findings showed that nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities were regulated in opposite ways during the processes associated with liver regeneration. Moreover, they suggested that the polyamines themselves might have a direct or indirect role in this regulation.
 ...
PMID:Opposite responses of nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities to regenerative stimuli in rat liver. 156 34

Chronic ethanol effect on regenerating post-partial hepatectomy rat liver was studied from 0 to 80 hr to evaluate sequential changes. The rate of restoration in liver mass was comparable between controls (C) and ethanol (E) treated rats. Cell cycle changes included a decrease in magnitude and duration of the early peak in DNA synthesis (24 hr). However, the second peak (40 hr) was increased in magnitude so that the net change was negligible. Histone synthesis increased markedly, whereas thymidine kinase activity was moderately increased. The net effect was an accelerated accumulation of DNA (0.18 mg of DNA/g liver/hr vs 0.29 mg of DNA/g liver/hr; C vs E). The M phase of the cell cycle was initially delayed by ethanol, but once initiated, it exhibited greater numbers of mitoses reaching significance at 72 hr. It is concluded that although ethanol induces multiple changes, the overall process of restoring liver mass and cell number (DNA synthesis) is not impaired.
 ...
PMID:Cell cycle and organelle enzyme changes in the regenerating liver of the alcoholic rat. 342 66

Liver regeneration is an essential component of the reparative process following liver injury and surgical resection. It can be assessed by different tissue-based tests such as liver weights, mitotic counts, DNA contents and synthesis rates, immunohistochemical staining of nuclear antigens, gene expressions and certain protein levels or various serum-based tests that largely consist of specific enzyme determinations or documentation of certain proliferation markers. Although the simplest tissue-based test of liver regeneration is measurement of liver weights, these determinations are influenced by the extent of deposition of various materials not directly related to regeneration, such as lipids, glycogen and blood volumes. Because mitosis constitutes a very short segment of the cell cycle, mitotic counts are infrequently observed by light microscopy. Thymidine and BrdU incorporation into DNA are the reference tools for studying DNA synthesis, but their use requires pre-injection with radioactive isotopes or nucleotides which render them impractical for human studies. Flow cytometry is an accurate and objective method of monitoring hepatic regenerative activity but requires sophisticated equipment that is not generally available in many laboratories. Immunohistochemical staining for nuclear antigens (Ki-67, proliferating cell nuclear antigen [PCNA], DNA polymerase alpha and nucleolar organizer region [NOR] proteins) are acceptable and commonly used methods of monitoring regenerative activity but are subject to inter- and intra-observer variability. Gene expression rates such as Histone-3 mRNA abundance are hampered by the relatively low rates of gene transcription and the need for recombinant DNA technology. Protein and enzyme levels in liver tissues, such as putrescine, ornithine decarboxylase and thymidine kinase, are not precise and are confounded by the nutritional status of the host. While PCNA protein levels measured by immunoblot hold promise as a simple, accurate and reproducible marker of liver regeneration, additional studies are required to determine if this is a valid marker of regenerative activity in various models of hepatic injury and in humans. Of the serum-based determinations: thymidine kinase, ornithine decarboxylase, fibronectin, alpha fetoprotein, and early pregnancy factor offer practical and non-invasive tools to monitor liver regeneration, but the sensitivity and specificity of these tests have yet to be determined. In conclusion, many tissue and serum-based methods have been employed in clinical and experimental studies to assess liver regeneration; however, a gold standard has yet to be identified. Because of the disadvantages inherent in each method, and until a new, more accurate marker is identified, clinicians and scientists should incorporate a minimum of two independent markers in studies of liver regeneration.
 ...
PMID:Liver regeneration: methods for monitoring and their applications. 912 13