Role of sirtuins in ischemia-reperfusion injury

Pantazi, Eirini

doi:10.3748/wjg.v19.i43.7594

Cited by 58 publications

(55 citation statements)

References 100 publications

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“…At the cellular level, SIRT1 is known as a nuclear protein, which is predominantly expressed in neurons. 21 In the current study, we further performed double immunofluorescent staining to evaluate the cellular distribution of SIRT1. Consistent with previous studies, 4, 12, 19 we showed that SIRT1 could be expressed in neurons and microglia, and the elevated SIRT1 after SAH was mainly located in the neurons in the rat brain cortex.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Activation of Sirt1 promotes the transcription of genes in the regulation of mitochondrial biogenesis to maintain energy and metabolic homeostasis (16, 17). Thus, modulation of Sirt1 activity in various disease conditions has been gaining traction and multiple studies have shown its beneficial effects in protecting various organs from I/R induced injury (18-22). …”

Section: Introductionmentioning

confidence: 99%

Sirtuin 1 Stimulation Attenuates Ischemic Liver Injury and Enhances Mitochondrial Recovery and Autophagy

Khader¹,

Yang²,

Godwin

et al. 2016

Critical Care Medicine

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Objective Hepatic ischemia-reperfusion (I/R) is a major clinical problem with limited treatment options. The pathophysiology of hepatic I/R is characterized by mitochondrial dysfunction and cellular energy deficits. Sirtuin 1 (Sirt1) is an energy-sensing enzyme known to modulate mitochondrial biogenesis. We hypothesized that pharmacologic activation of Sirt1 is protective after hepatic I/R injury. Design Animal study. Setting University-based experimental laboratory. Subjects Wild-type C57BL/6 mice. Interventions C57BL/6 mice were subjected to 60-min partial hepatic I/R and post-treated with Sirt1 activator, SRT1720 (20 mg/kg), or vehicle. Blood and liver were collected at 24 h after I/R for analyses of hepatic injury, ATP levels, mitochondrial mass, autophagy, inflammation, and oxidative stress. H4IIE hepatoma cells and rat primary hepatocytes were incubated with oxyrase to induce hypoxia followed by reoxygenation (H/R) in the presence or absence of SRT1720 for assessment of mitochondrial mass, mitochondrial membrane potential, and autophagy. Measurements and Main Results SRT1720 restored the reduction in mitochondrial mass, enhanced autophagy, and preserved ATP levels in the liver after I/R, which was associated with a decrease in I/R-induced hepatic injury, apoptosis, and necrosis. I/R-induced inflammation was also significantly reduced by SRT1720 as measured by systemic and hepatic cytokine and chemokine levels as well as a decrease in neutrophil infiltration to the liver. Further, oxidative stress was markedly attenuated in the SRT1720-treated mice, compared to the vehicle. SRT1720 treatment increased ATP levels and survival of cultured hepatocytes after H/R. SRT1720 not only increased the mitochondrial mass but also increased mitochondrial membrane potential per cell in cultured hepatocytes after H/R. Moreover, SRT1720 prevented the H/R-induced mitochondrial depolarization and resulted in an enhancement of autophagy in cultured hepatocytes after H/R. Conclusions Pharmacologic stimulation of Sirt1 attenuates liver injury after hepatic I/R by restoring mitochondrial mass and membrane potential, which is associated with the enhancement of autophagy.

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“…It will be important to develop experimental models in which the levels of oxidative stress and the activities of sirtuins can be precisely modulated to determine how sirtuins have a causative role in lifespan extension. Also, the role of sirtuins in the cardiovascular system has been investigated (Cencioni et al 2015;D'Onofrio et al 2015;Pantazi et al 2013), and sirtuins appear to have a prominent role in cardiovascular biology and may regulate aspects of cardiovascular health and age-dependent CVDs.…”

Section: The Sirtuin Familymentioning

confidence: 99%

Sirtuins, aging, and cardiovascular risks

Favero

Franceschetti

Rodella

2015

AGE

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The sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class III histone deacetylases, and seven sirtuin genes (sirtuins 1-7) have been identified and characterized in mammals. Sirtuin activity is linked to metabolic control, apoptosis, cell survival, development, inflammation, and healthy aging. In this review, we summarize and discuss the potential mutual relations between each sirtuin and cardiovascular health and the impact of sirtuins on oxidative stress and so age-related cardiovascular disorders, underlining the possibility that sirtuins will be novel targets to contrast cardiovascular risks induced by aging.

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Role of sirtuins in ischemia-reperfusion injury

Cited by 58 publications

References 100 publications

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

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

Sirtuin 1 Stimulation Attenuates Ischemic Liver Injury and Enhances Mitochondrial Recovery and Autophagy

Sirtuins, aging, and cardiovascular risks

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