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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Effect of Insulin on DNA-Internucleosomal Fragmentation and Poly(ADP-ribose)polymerase 1 Activity in Rat Liver Nuclei

Apoptosis is the main type of physiological cell death which ensures tissue homeostasis by a dy¬na¬mic balance between cell proliferation and death. The final and “point of no return” phase of apoptosis is DNA internucleosomal frag¬men¬tation resulting in effective degradation of the nuclear DNA and its further elimination by pha¬gocytes [1]. Peptide hor¬¬mones along with various intra- and extracellular signals tightly regulate the onset of apoptosis by modulating tissue and cell-specific responses. Liver is a target organ where insulin displays antiapoptotic properties. One of the key factors which mediates the cross-talk of various death path¬ways is poly(ADP-ribose)polymerase 1 (PARP 1), the activity of which is precisely re¬gu¬lated by different exogenous and endogenous cell signals. The activation of PARP 1 by DNA strand breaks and inhibition of the enzyme by ATP, establishes PARP 1 as a molecular link bet¬ween DNA damage, energy status and chromatin modification in cells [2,3]. PARP 1 plays a prominent role in switching different cell death programs by distinct mechanisms: depleting intracellular NAD+ and ATP, controlling chromatin accessibility and the activities of various apoptotic en¬do¬¬nucleases, which are required for normal nuclear degradation. In present study we examined whether insulin can modulate the key process of execution phase of apoptosis - internucleosomal DNA fragmentation, in isolated rat liver nuclei after 4 and 24 hours during hormone administration to rats. The activity of PARP 1 was concomitantly investigated. Our results revealed that insulin suppressed the intensity of DNA fragmentation twofold after 4 hours of injection. Nevertheless, during 24 hours insulin markedly stimulated DNA internucleosomal fragmentation. However, insulin had no appreciable effect on PARP 1 activity in rat liver nuclei in all examined periods of hormone action. Taking into consideration, that the activity of PARP 1 depends on ability of the enzyme molecules to bind DNA, we suppose that hydrocortisone’s nuclear receptor can modulate PARP 1 activity by competing with the enzyme for binding sites on DNA.

References

    1. S. Elmore. (2007) Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol. 35. 495-516.

    2. M.Y. Kim, T. Zhang & W.L. Kraus. (2005). Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes & Development 19. 1951-1967.

    3. P.O. Hassa & M.O. Hottiger. (2008). The diverse biological roles of mammalian PARPs, a small but powerful family of poly-ADP-ribose polymerases. Frontiers in Bioscience 13. 3046-3082.

Anush Asatryan
Karine Matinyan
Irina Artsruni
Emil Gevorgyan

Department of Biophysics
Yerevan State University
Yerevan, Armenia, 0025

Ph: (374)91180810
Email: anush.asatryan@ysu.am