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Journal Article 2011; 32(3): 313-316 PubMed PMID: 21712774 Citation  Keywords:  Amyloid Precursor Protein Secretases:biosynthesis, Amyloid beta-Peptides:biosynthesis, Amyloid beta-Protein Precursor:biosynthesis, Aspartic Acid Endopeptidases:biosynthesis, Cell Line, Cells, Cultured, DNA:biosynthesis, Humans, Luciferases:genetics, RNA,.   

OBJECTIVE: The effect of SUMO on the promoter activity and mRNA expression of BACE gene was investigated to find the connection between sumoylation and APP processing.

METHODS: The BACE promoter activity was measured by reporter gene analysis and BACE mRNA level was investigated using real-time RT-PCR method.

RESULTS: BACE gene promoter activity was inhibited by the over-expression of SUMO proteins and was blocked by disrupting the SP1 site. Endogenous BACE mRNA level was also negatively regulated by the induction of SUMO proteins. Using a specific inhitor of SP1, BACE promoter activity was coordinately inhibited.

CONCLUSIONS: SUMO negatively regulates the BACE expression and SP1 is involved in the process....

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Journal Article 2008; 29(5): 653-657 PubMed PMID: 18987576 Citation  Keywords:  Adenomatous Polyposis Coli:epidemiology, Adenomatous Polyposis Coli Protein:genetics, Chromatography, High Pressure Liquid, DNA:biosynthesis, Gene Deletion, Mutation, Polymorphism, Single-Stranded Conformational:genetics, Reverse Transcriptase Polymerase .   

OBJECTIVES: The adenomatous polyposis coli (APC) gene was analyzed for germline mutations in 113 familial adenomatous polyposis suspected families from all over Slovakia. Mutation screening was performed using single strand conformation polymorphism (SSCP) and DNA sequencing.

RESULTS: Mutations in the APC gene were found in 39 (34.5%) Slovak families and 25 different pathogenic mutations throughout the APC gene were identified. Of these, 12 mutations were deletion, one was insertion and 12 were base substitution.

CONCLUSIONS: Molecular diagnostics of Slovak FAP families revealed broad palette of mutations in crucial APC gene. The patients with identified APC gene mutations were assigned to a specific therapeutic FAP program....

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Journal Article 2003; 24(3-4): 215-223 PubMed PMID: 14523360 Citation  Keywords:  Aging:metabolism, Animals, Autoradiography, Cell Division:drug effects, DNA:biosynthesis, Male, Melatonin:pharmacology, Microscopy, Electron, Rats, Rats, Sprague-Dawley, Spleen:cytology, T-Lymphocytes:drug effects, Thymus Gland:drug effects,.   

OBJECTIVES: In this study we investigated the effect of melatonin treatment on the proliferative activity, the rate of DNA synthesis and the histopathological changes of splenic and thymic lymphocytes in old rats.

METHODS: Two subgroups of old rats (25-months-old) were used in this study. One subgroup was given melatonin in the drinking water (250-300 mg/day/rat) for 3 months while the second subgroup was given water containing diluent. A third group consisted of young rats (3-months-old) which served as an additional control.

RESULTS: A (3)H-thymidine autoradiographic investigation showed a reduction in both the proliferative activity and the rate of DNA synthesis in splenic and thymic lymphocytes in old rats. In addition, light and electron microscopy showed severe histopathological changes in these cells from diluent-treated old rats. Melatonin administration increased the proliferative activity and the rate of DNA synthesis in the lymphocytes of both the spleen and thymus of the old animals. Also, histopathological changes were partially reversed by melatonin treatment with the tissues appearing similar to those in the young rats.

CONCLUSION: The stimulation of the lymphocyte activity by melatonin is a beneficial response, especially in old rats, since aging results in an inhibition in lymphocytic functions....

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Journal Article 2002; 23(4): 335-340 PubMed PMID: 12195237 Citation  Keywords:  Animals, Anticonvulsants:pharmacology, Cell Division:drug effects, DNA:biosynthesis, Drug Interactions, Hepatocytes:drug effects, Male, Melatonin:pharmacology, Mutagens:pharmacology, Necrosis, Nitroparaffins:pharmacology, Propane:analogs & derivatives, Ra.   

OBJECTIVES: 2-Nitropropane (2-NP) is mutagenic in a number of short-term mutagenicity assays in vitro and in vivo, and is a potent hepatocarcinogen in rats. Many studies have determined that differences in the metabolism and disposition of the chemicals that produce mutagenicity were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ.

METHODS: Three groups of male rats (control, 2-NP-treated [4 mmol/kg] and 2-NP + melatonin [10 mg/kg]) were used in the current study. Cell proliferation was quantitated by incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Histopatholgical study was carried out to investigate the morphological changes.

RESULTS: Twenty four hours after 2-NP administration, there was an increase in the labelling index (LI) and grain count per labelled nucleus (GC/N) in the hepatocytes of 2-NP-injected rats versus those of control animals. The increase was 69.5% in LI and 29.4% in GC/N. Melatonin treatment, 30 minutes preceding 2-NP, reduced the increase in LI (44.4%) and GC/N (20.7%) when compared with 2-NP-treated rats. Histopathology revealed multiple focal areas of necrosis in the liver following 2-NP injection. In the lung, there was a mucinous degeneration of the bronchial epithelium. Melatonin treatment restored the histopathological changes in both the liver and lung and they are more or less normal.

CONCLUSION: Overall, these results seem to indicate that the stimulatory effect of 2-NP on the cellular proliferation and the rate of DNA synthesis in the liver may be one of mechanisms by which the carcinogen induces its carcinogenic action. Also, melatonin treatment strongly protects the studied organs against the toxic effect of 2-NP....

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