Regulation of apoptosis under influence of poly[ADP-ribose] polymerase-1

Kekić, Tadija (2012) Regulation of apoptosis under influence of poly[ADP-ribose] polymerase-1. Bachelor's thesis, Faculty of Science > Department of Biology.

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Abstract

Apoptotic cell death is an active process involving specific enzymes capable of cleaving DNA into nucleosome-sized fragments. Poly (ADP-ribosylation) is a post-translational modification, which performs a role in repair of DNA damage, DNA replication, viral integration and modulation of this process which occurs during programmed cell death. Poly (ADP-ribose)polymerase-1 is involved in the path of cell death which is caspasedependent, but also in one that is independent, in which an important role belongs to apoptosis induction factor (AIF). In the caspase-dependent way, in the egzecution stage, PARP-1 is inactivated and cleaved by caspase 3 and 7 that separate the PARP-1 DNA binding domain from its catalytic domain. Inactivation of PARP-1 is a way to save energy because it reduces consumption of NAD + and ATP. If the cells activated PARP-1, and would not have enough energy to carry out a process of apoptosis, it is possible that PARP-1 will lead the cell towards necrosis. PARP-1 activators, including N-methyl-N'-nitro-N-nitroguanidin (MNNG), hydrogen peroxide and NMDA, induces translocation of AIF from mitochondria to nucleus, leading to cell death. The AIF-cell death pathway does not halt characteristic events by caspase inhibitors, but rather by inhibitors of PARP-1 or PARP-1 knockout cell lines. Therefore, the cell death caused by translocation of AIF-dependent poly(ADP-ribozyl)ation. How poly(ADP-ribozyl)ation regulates AIF, through lack of NAD + or PAR, or AIF release from mitochondria is not yet known. Activity of the enzyme PARP-1 can be stoped by chemicals, overexpression of PARP DNA binding domains, and gene silencing using antisense RNA. Learning about these types of inhibition can assist in the creation of new, more effective drugs in chemotherapy. Today it has many studies that analyze the link between the various processes in apoptosis, but based on current information obtained by studying the activities of PARP-1 is influenced stimuli we can not form a general model of apoptosis.

Item Type: Thesis (Bachelor's thesis)
Supervisor: Matulić, Maja
Date: 2012
Number of Pages: 19
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 23 Oct 2014 12:46
Last Modified: 23 Oct 2014 12:46
URI: http://digre.pmf.unizg.hr/id/eprint/3154

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