Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA260

Poster Communications

SIRT2 inhibition suppresses the oxidative stress and apoptotic activity, and increases autophagy of cerebral cortex in the aging process.

K. G. Akbulut1, A. Keskin-Aktan1,3, S. Abgarmi2, H. Akbulut2

1. Physiology, Gazi University, Ankara, Turkey. 2. Internal Medicine, Ankara University School of Medicine, Ankara, Turkey. 3. Physiology, Nuh Naci Yazgan Unversity Health Science Faculty, Kayseri, Turkey.

Increased oxidative stress in the elderly is accompanied by apoptosis1. Autophagy declines with age2. Likewise, an increase in the level of oxidative stress and apoptosis, and a decrease in autophagy are closely related to neurodegenerative diseases3. It has been shown that sirtuin 2 (SIRT2) expression in the cerebral cortex increases in the elderly and inhibition of SIRT2 can prevent neurodegenerative diseases4. In this study, we aimed to study the role of SIRT 2 expression on oxidative stress, apoptotic activity and autophagy of the cerebral cortex in the young and aged rats. In the study, 6 groups were formed by using 36 Wistar albino rats (3-month old, n = 18, 22-month old n = 18): Young (injected with PBS), Young-Control (injected with 4% DMSO), Young-AGK-2 (injected with AGK-2 dissolved in 4% DMSO, a specific SIRT 2 inhibitor), Aged, Aged-Control, and Aged-AGK-2. The injections of the control and experimental groups were maintained for 30 days. On the 31st day of the experiment, rats were sacrificed and the cerebral cortex was isolated. Total oxidant status (TOS) and total antioxidant status (TAS) measurements were made using commercial kits and the oxidative stress index (OSI) obtained by the ratio of TOS to TAS. BCL-2, BAX expressions were studied as apoptosis parameters, beclin and ATG-5 as autophagy by Western blotting and real-time PCR. Student's T, Two-way ANOVA and Pearson's r were used for statistical analysis (p <0.05). Our findings showed that aging decreased the BCL-2, BCL-2 / BAX ratio, beclin and TAS in the cerebral cortex and increased the TOS and OSI. We found that SIRT 2 inhibition by AGK-2 administration reduced cortical TOS and OSI levels, and increased BCL-2, BCL-2 / BAX ratio and beclin in aged animals. As a result, SIRT2 inhibition by AGK-2 may suppress oxidative stress and apoptotic activity, and increases autophagy. SIRT 2 could be a therapeutic target for the prevention of neurodegenerative diseases in the elderly.

Where applicable, experiments conform with Society ethical requirements