Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats

Abstract

Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH.

Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

“…In our study, Western blotting revealed that consecutive superovulation decreased the SIRT1 and FOXO1 levels in a cycle number-dependent manner. Several lines of evidence support this result and indicate that SIRT1 plays a key role in the adaptive responses of cells to a variety of oxidative stressors [88, 90]. The SIRT1/FOXO1 pathway may be a crucial regulator of apoptosis and oxidative stress resistance, consistent with the findings of previous reports [91, 92].…”

“…Sirtuins suppress age-related dysfunction and increase longevity by increasing SIRT1 expression [86, 87]. FOXO1 is deacetylated by SIRT1 to evoke cellular resistance to stress by promoting the expression of antioxidant enzymes that detoxify ROS or induce cell cycle arrest to allow time for DNA repair and other repair processes [88, 89]. In our study, Western blotting revealed that consecutive superovulation decreased the SIRT1 and FOXO1 levels in a cycle number-dependent manner.…”

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

“…7G and 8G). Several lines of evidence support this result and indicate that SIRT1 plays a key role in the adaptive responses of cells to a variety of oxidative stressors by deacetylating several FOXO members [17, 38]. Earlier research also revealed that FOXO1 is one of the FOXO proteins and that its transcriptional activity is modulated by SIRT1 [39].…”

“…In mammalian cells, acetylation of FOXO1 increases in response to oxidative stress. FOXO1 can be deacetylated by SIRT1 to evoke cellular resistance to stress by promoting antioxidant enzymes that detoxify ROS or inducing cell cycle arrest to allow time for DNA repair and other repair processes [17, 18]. …”

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

“…SIRT1 pathways are involved in vascular survival and senescence (88, 152, 161), atherosclerosis (162–166), lifespan extension (4, 167–169), diabetic retinopathy (170), cellular metabolism and DM (14, 17, 20, 115, 145, 171, 172), oxidative stress pathways (58, 148, 173–179), and neuronal survival and cognition (11, 113, 180–183). …”