The role of melatonin, sirtuin2 and FoXO1 transcription factor in the aging process of colon in male rats

Abstract

The protein family of sirtuins and FoXO1 transcription factor have been shown to play significant roles in the aging process. In this study we aimed to investigate the changes in the levels of SIRT2, NFκB and FoXO1 and oxidative parameters of colonic mucosa during aging, and the effects of exogenous melatonin (MLT). A total of twenty-four young (3-months-old) and aged (24 months old) male Wistar rats, divided into control [1% ethanol--phosphate-buffered saline (PBS), s.c. for 21 days] and melatonin (10 mg kg(-1) MLT 1% ethanol in PBS, s.c. for 21 days) were used in the study. The levels of malondialdehyde (MDA) as a parameter of lipid peroxidation, glutathione, NFkB pathway activation, SIRT2 expression, and FoXO1 transcription factor of colonic mucosa were assayed. The MDA levels and SIRT2 expression in the colonic mucosa were significantly increased in the aged group when compared to the younger group. However, the levels of FoXO1 transcription factor were significantly decreased in the aged group. Melatonin significantly decreased the MDA and SIRT2 expression levels of the colonic mucosa in the aged rats. In conclusion, our findings suggest a suppressive role of melatonin in the aging process of colonic tissue via decreasing SIRT2 expression.

Melatonin protects against maternal obesity‐associated oxidative stress and meiotic defects in oocytes via the SIRT3‐SOD2‐dependent pathway

“…Melatonin levels decreases with age in serum; this loss may be related to increased age‐associated pathologies . Treatment of old rats with melatonin not only reduced oxidative stress but also concomitantly increased SIRT2 expression . Melatonin attenuates myocardial ischemia/reperfusion injury via activation of SIRT3 signaling in a receptor‐dependent manner .…”

MicroRNA-212-5p Prevents Dopaminergic Neuron Death by Inhibiting SIRT2 in MPTP-Induced Mouse Model of Parkinson’s Disease

“…Unlike SIRT1, SIRT2 is present primarily in the cytoplasm, co-localizes with microtubules and deacetylates the major component of microtubules, α-tubulin at lysine 40 ( North et al, 2003 ). In addition, SIRT2 deacetylates forkhead transcription factors of class O (FOXO) ( Wang et al, 2007 ; Pais et al, 2013 ; Akbulut et al, 2015 ) and NF-κB ( Li et al, 2013 ), as results of affecting apoptosis and inflammation. Moreover, sirtuin 2 is reported to exacerbate alpha-synuclein toxicity in models of Parkinson’s disease ( de Oliveira et al, 2017 ).…”

Emerging Role of Sirtuin 2 in Parkinson’s Disease

“…Within the G2/M phase of mitosis, SIRT2 is transferred from the cytoplasm to the nucleus where it deacetylates histone H4 at lysine 16, thus reducing the level of H4K16 acetylation, which in turn decreases chromatin condensation and facilitates DNA replication, but the specifical role in the pathogenesis of PD is not clear (Vaquero et al, 2006). In addition, SIRT2 also shuttles to the nucleus in response to cellular stress and is capable of deacetylating the forkhead box class O (FOXO) family of transcription factors, which are pivotal in a myriad of physiological processes (Wang et al, 2007;Pais et al, 2013;Akbulut et al, 2015). Under oxidative stress, SIRT2 releases FOXO1, which is then being acetylated and able to bind to ATG7, eventually contributing to autophagy in cancer (Zhao et al, 2010a).…”