Regulacija apoptoze pod utjecajem poli[ADP-riboza] polimeraze-1

undergraduate thesis

• Title (english): Regulation of apoptosis under influence of poly[ADP-ribose] polymerase-1
• Author: Tadija Kekić
• Mentor: Maja Matulić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2012, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Apoptotička smrt stanice je aktivan proces koji uključuje specifične enzime sposobne da cijepaju DNA u fragmente veličine nukleosoma. Poli(ADP-ribozilacija) je post-translacijska modifikacija koja vrši ulogu u popravku oštećenja DNA, DNA replikaciji, viralnoj integraciji, a modulacija ovog procesa događa se tijekom programirane stanične smrti. Poli(ADP-riboza)polimeraza-1 je uključena u put stanične smrti koji je ovisan o kaspazama, ali i u onaj koji je neovisan, u kojem važnu ulogu ima i... More faktor indukcije apoptoze (AIF). U kaspaza-ovisnom putu, u egzekucionoj fazi, PARP-1 je inaktiviran i pocijepan kaspazama 3 i 7 koje razdvajaju PARP-1 DNA veznu domenu od njegove katalitičke domene. Inaktivacija PARP-1 je način uštede energije jer se tako smanjuje potrošnja NAD+ i ATP-a. Ukoliko bi stanica aktivirala PARP-1, a ne bi imala dovoljno energije za izvršenje procesa apoptoze, tada je moguće da bi PARP-1 usmjerio stanicu u nekrozu. PARP-1 aktivatori uključujući N-metil-N'-nitro-N-nitroguanidin (MNNG), vodikov peroksid i NMDA induciraju translokaciju AIF iz mitohondrija u nukleus što dovodi do stanične smrti. U AIF putu stanične smrti ne dolazi do zaustavljanja karakterističnih događaja od strane inhibitora kaspaza, već od inhibitora PARP-1 ili u PARP-1 knockout staničnim linijama. Stoga, je stanična smrt uzrokovana translokacijom AIF ovisna o poli(ADP-ribozil)aciji. Kako poli(ADP-ribozil)acija regulira AIF, preko nedostatka NAD+ ili PAR ili otpuštanjem iz mitohondrija, još nije poznato. Aktivnost enzima PARP-1 se može zaustavljati kemikalijama, overekspresijom PARP DNA veznih domena, utišavanjem gena i korištenjem antisense RNA. Saznanja o ovim vrstama inhibice može pomoći prilikom stvaranja novih, efikasnijih lijekova u kemoterapiji. Danas se vode mnoga istraživanja koja analiziraju poveznicu između različitih procesa unutar apoptoze, ali na temelju trenutnih informacija dobivenih proučavanjem aktivnosti PARP-1 pod utjecajem različitih stimulansa apoptoze ne možemo formirati generalni model apoptoze. Less

Abstract (english)

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... More 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. Less

• Keywords: apoptoza; poli(ADP-riboza)polimeraza-1
• Keywords (english): apoptosis; poly[ADP-ribose] polymerase-1
• Language: croatian
• URN:NBN: urn:nbn:hr:217:948110
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-04-17 12:53:36