Ukr.Biochem.J. 2019; Volume 91, Issue 1, Jan-Feb, pp. 21-29


Altered sirtuins 1 and 2 expression in the brain of rats induced by experimental diabetes and the ways of its correction

M. M. Guzyk1, T. M. Tykhonenko1, K. O. Dyakun1,
L. V. Yanitska2, I. B. Pryvrotska3, T. M. Kuchmerovska1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Bogomolets National Medical University, Kyiv, Ukraine;
3I. Horbachevsky Ternopil State Medical University, Ukraine;

Received: 03 August 2018; Accepted: 13 December 2018

The molecular pathogenesis of diabetic encephalopathy (DE), one of the serious complications of diabetes mellitus, is complex. In this study, we examined whether expression levels of SIRT1 and SIRT2 were the key for the development of brain dysfunctions and whether PARP-1 inhibitors could affect the expression of these proteins for prevention the development of DE in rats with type 1 diabetes. After 10 weeks of the streptozotocin-induced diabetes mellitus (70 mg/kg), Wistar male rats were treated by i.p. injection with PARP-1 inhibitors, 1.5-isoquinolinediol (ISO) or nicotinamide (NAm) (3 or 100 mg/kg/daily i.p., respectively) for 2 weeks. The rats with blood glucose levels over 19.7 ± 2.1 mmol/l were taken into experiments. Western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of sirtuins, SIRT1 and SIRT2 expression. Diabetes induced significant reduction of SIRT1 expression and SIRT2 overexpression in brain nuclear extracts of diabetic rats compared to non-diabetic control. In brain, NAm attenuated SIRT2 overexpression in nuclear extracts of diabetic rats and slightly elevated SIRT1 expression, while ISO didn’t affect expression of both sirtuins in diabetic rats. Furthermore, it was observed that in brain of diabetic rats, the ratio of free NAD/NADH couples decreased 3.1-fold compared to non-diabetic control. The administration of ISO increased only slightly the ratio of free NAD/NADH couples in the brain of diabetic rats while NAm increased this parameter 1.7-fold compared to diabetic rats. Therefore, we concluded that alterations in the expression of SIRT1 and SIRT2 in brain cell nuclei of diabetic rats can lead to the development of brain dysfunctions. One of the neuroprotective mechanisms of NAm action can also be realized through inhibition of SIRT2 expression in brain cell nuclei that down-regulate progression of diabetes-induced alterations and can be a therapeutic option for treatment of brain dysfunctions.

Keywords: , , , , , ,


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