engleski

Poly(ADP)ribose polymerase in the biology of glioblastoma cells

Poly(ADP)polymerase-1 (PARP-1) is a nuclear protein involved in the posttranslational process of poly(ADPribos)ylation, synthesis of ADP-ribose polymer on target proteins. It has an important role in maintaining genome integrity. Its enzymatic activity is highly induced by DNA strand breaks, when it recruits damage repair proteins to the DNA. PARP-1 has also a role in the regulation of transcription and chromatin structure, as well as in DNA methylation. In our study we investigated the role of PARP-1 in the biology of the A1235 human glioblastoma cell line. Cells were treated with sublethal doses of alkylating agent N-methyl-N'-nitro- N-nitrosoguanidine (MNNG), either alone or in combination with PARP-1 inhibitor. We analyzed cell proliferation, appearance of senescent cells, changes in cell morphology, cell cycle and effects on the urokinase plasminogen activator induction. Although PARP-1 inhibitors slightly decreased cell proliferation when added with MNNG in comparison with the alkylating agent alone, both treatments similarly affected cell cycle (accumulation of cells in S and G2 cell cycle phase) and also induced senescence. On the other side, activity of the extracellular protease, urokinase plasminogen activator, known to be induced in A1235 cells by alkylating agents, was modulated by the PARP-1 inhibitor. The mechanisms of PARP-1 regulation in the process of transcription will be discussed.

poly(ADP)ribose polymerase

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