Wyniki wyszukiwania - Biblioteka Nauki

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Gdansk Library of the Polish Academy of Sciences

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Pętlicka W. , Tylewska-Ostrowska Z. , Walczak A. , Pętlicka W. , Tylewska-Ostrowska Z. , Walczak A.

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Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer

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Kabziński J. , Walczak A. , Mik M. , Majsterek I.

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tom 92(1)

1-4

EN

Colorectal cancer (CRC) is one of the most common malignant tumors. One of the factors increasing the risk of its occurrence may be the reduced efficiency of repairing DNA damage, both nuclear and mitochondrial. The main mechanism for repairing oxidative damage is the BER system (in mitochondria mtBER), whose key proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 obtain full efficiency only at the appropriate level of acetylation. Sirtuin 3 is a key protein for mitochondrial homeostasis, regulating a number of metabolic processes related mainly to the control of the level of reactive oxygen species. Because Sirt3 possesses acetylase activity, it can modulate the level of activity of mtBER proteins by their deacetylation. The conducted study showed that the tested proteins NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 are the substrate for the enzymatic deacetylation activity of Sirt3, which may lead to modulation of the risk of CRC, and in cancer cells may be a potential therapeutic target enhancing the action of cytostatic drugs.

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Impact of the Ser326Cys polymorphism of the OGG1 gene on the level of oxidative DNA damage in patients with colorectal cancer

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Kabzinski J. , Walczak A. , Dziki A. , Mik M. , Majsterek I.

Polish Journal of Surgery

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2018

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tom 90(2)

13-15

EN

As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG. Linking individual polymorphisms to DNA repair systems with increased risk of colorectal cancer will allow patients to be classified as high risk and included in a prophylactic program. The aim of the study was to determine the level of oxidative DNA damage and to analyze the distribution of Ser326Cys polymorphism of the OGG1 gene in a group of patients with colorectal cancer and in a control group in the Polish population. Material and methodology. DNA was isolated from the blood of 174 patients with colorectal cancer. The control group consisted of 176 healthy individuals. The level of oxidative damage was determined by analyzing the amount of 8-oxguanine using the HT 8-oxo-dG ELISA II Kit. Genotyping was performed via the TaqMan method. Results. The obtained results indicate that Ser326Cys polymorphism of the OGG1 gene increases the risk of RJG and is associated with significantly increased levels of 8-oxoguanine. Conclusions. Based on the results obtained, we conclude that Ser326Cys polymorphism of the OGG1 gene may modulate the risk of colorectal cancer by increasing the level of oxidative DNA damage.

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Wpływ polimorfizmu Ser326Cys genu OGG1 na poziom uszkodzeń oksydacyjnych DNA u pacjentów z rakiem jelita grubego

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Kabzinski J. , Walczak A. , Dziki A. , Mik M. , Majsterek I.

Polish Journal of Surgery

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2018

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tom 90(2)

13-15

PL

W wyniku działania reaktywnych form tlenu na komórki dochodzi do szerokiego zakresu uszkodzeń zarówno organelli komórkowych, jak i cząsteczek, w tym DNA. Uszkodzenia oksydacyjne w obrębie materiału genetycznego prowadzić mogą do akumulacji mutacji i w konsekwencji do transformacji nowotworowej. Glikozylaza OGG1 – składowa systemu naprawy Base Excision Repair (BER) – to jeden z enzymów zapobiegających nadmiernej akumulacji 8-oksoguaniny (8-oxG), która jest najczęstszym związkiem powstającym w wyniku oksydacyjnego uszkodzenia DNA. W przypadku zmian strukturalnych OGG1 wynikających z wariantów polimorficznych obserwować możemy znaczący wzrost stężenia 8-oxG. Powiązanie poszczególnych polimorfizmów systemów naprawy DNA ze zwiększonym ryzykiem raka jelita grubego pozwoli na kwalifikację pacjentów do grup podwyższonego ryzyka i objęcie ich programem profilaktycznym. Cele pracy: Określenie poziomu uszkodzeń oksydacyjnych DNA oraz analiza rozkładu polimorfizmu Ser326Cys genu OGG1 w grupie pacjentów z rakiem jelita grubego i w grupie kontrolnej w populacji polskiej. Materiał i metody: Jako materiał wykorzystano DNA wyizolowane z krwi pobranej od 174 pacjentów ze zdiagnozowanym rakiem jelita grubego. Grupę kontrolną stanowiło 176 zdrowych osób. Poziom uszkodzeń oksydacyjnych określono na podstawie analizy ilości 8-oksguaniny, używając HT 8-oxo-dG ELISA II Kit. Genotypowanie przeprowadzono metodą TaqMan. Wyniki: Uzyskane wyniki wskazują, iż polimorfizm Ser326Cys genu OGG1 zwiększa ryzyko występowania RJG oraz jest powiązany ze znacząco zwiększonym poziomem 8-oksoguaniny. Wnioski: Na podstawie uzyskanych wyników wnioskujemy, że polimorfizm Ser326Cys genu OGG1 może modulować ryzyko występowania raka jelita grubego poprzez zwiększony poziom uszkodzeń oksydacyjnych DNA.

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The -2518 A/G MCP-1 polymorphism as a risk factor of inflammatory bowel disease

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Walczak A. , Przybyłowska K. , Sygut A. , Dziki Ł. , Chojnacki C. , Chojnacki J. , Dziki A. , Majsterek I.

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2012

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tom 84(5)

238-241

EN

Inflammatory bowel diseases (IBD) are disorders originated from immune disturbances. The aim of the study was to evaluate the association between the -2518 A/G MCP-1 polymorphism and the risk of IBD development. Material and methods. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Study group consisted of 197 subjects with IBD (120 with ulcerative colitis and 77 with Crohn’s disease) as well as 210 healthy controls. Results. The presence of the -2518 G/G MCP-1 genotype in the investigated groups seems to be connected with higher risk of inflammatory bowel disease as well as Crohn’s disease only (OR 2.26; 95% CI 1.44-3.54 and OR 2.08; 95% CI 1.21-3.46, respectively). Conclusions. Our data showed that the -2518 A/G MCP-1 polymorphism might be associated with the IBD occurrence and might be used as predictive factor of these diseases in a Polish population.

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An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence

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Walczak A. , Przybyłowska-Sygut K. , Sygut A. , Cieślak A. , Mik M. , Dziki Ł. , Dziki A. , Majsterek I.

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tom 89(5)

1-5

EN

The aim of the study: We evaluated the connection between the presence of the -2518 A/G MCP-1 as well as 190 G/A CCR2 polymorphic variants and colorectal cancer (CRC) occurrence. Material and methods: Study group consisted of subjects with different stages of CRC as well as healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: W observed an association between the colorectal cancer and the GG genotype of the -2518 A/G MCP-1 single nucleotide polymorphism. No statistically significant correlation was found between CRC and the 190 G/A CCR2 polymorphism. Conclusion: The results of this study support the hypothesis that polymorphism in the MCP-1 gene may contribute to the etiology of colorectal cancer.