Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

Chen, Tao; Dai, Shuhui; Li, Xia; Luo, Peng; Zhu, Jie; Wang, Yuhai; Zhou, Fei; Jiang, Xiaofan

doi:10.1016/j.redox.2017.09.016

Cited by 114 publications

(70 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Resveratrol reduces neuronal oxidative stress, attenuates calcium overload, inhibits endoplasmic reticulum (ER) stress and blocks mitochondrial apoptosis. 29,30 In addition, the inhibitory action of resveratrol on mitochondrial fission has been reported in several careful studies. Interestingly, no studies have investigated the role of resveratrol in Mfn1-mediated mitochondrial protection.…”

Section: Introductionmentioning

confidence: 95%

“…Ample evidence supports its therapeutic effects on reperfused brains. Resveratrol reduces neuronal oxidative stress, attenuates calcium overload, inhibits endoplasmic reticulum (ER) stress and blocks mitochondrial apoptosis . In addition, the inhibitory action of resveratrol on mitochondrial fission has been reported in several careful studies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

View full text Add to dashboard Cite

Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

show abstract

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

View full text Add to dashboard Cite

show abstract

“…Phosphorylated CREB translocates into the nucleus where it interacts with and activates the promoter of Mfn2, leading to the upregulation of Mfn2 expression and mitophagy activity (Fernandez Vazquez, Reiter, & Agil, ). Considering these results, the aim of the current study was to explore the protective role of Mfn2‐related mitophagy and its upstream regulatory mechanism in endothelial cell mitochondrial apoptosis following ox‐LDL injury (T. Chen, Dai, et al, ; Guan, Ding, & Wang, ). Taken together, the aim of our study is to figure out whether phosphatase and tensin homolog (PTEN) could modulate mitophagy activity via the AMPK–CREB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMPactivated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway. K E Y W O R D S AMPK-CREB-Mfn2 signaling pathway, endothelial cell dysfunction, Mfn2, mitophagy, ox-LDL, PTEN

show abstract

“…SIRT3 is a substrate for SIRT1 deacetylation and therefore its activation level may be directly modulated by SIRT1 (Kwon et al, 2017). In addition, they deacetylate some homologous substrates present in their corresponding cell compartments, nucleus and mitochondria (Hirschey et al, 2011), and may act cooperatively in response to inducing factors (Bell and Guarente, 2011) or against pathological conditions (Kwon et al, 2017;Chen et al, 2018). Therefore, we propose that the maintenance of the SIRT1-SIRT3 axis functionality, both in the brain and peripheral tissues, is a molecular mechanism that contributes to the acquisition of resilience through long-term physical activity.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Maintenance of the Axis SIRT1-SIRT3 at Youth Level May Contribute to Brain Resilience in Middle-Aged Amateur Rugby Players

Corpas

Solana

Rosa

et al. 2019

Front. Aging Neurosci.

View full text Add to dashboard Cite

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players (n = 24) and control subjects with low physical activity (n = 25) aged 45-65 years. We had previously reported neuropsychological improvement in immediate memory responses in the player group compared to the controls. Here, we tested the expression of selected genes of longevity, inflammation, redox homeostasis, and trophic signaling in whole blood mRNA. Analyses were also performed on blood samples of young (aged 15-25 years) control subjects with low physical activity (n = 21). Physical activity and other lifestyle factors were thoroughly recorded with standardized questionnaires. Interestingly, middle-aged control subjects showed lower levels of expression of SIRT1, SIRT3, CAT, and SOD1 than the young controls, although rugby players maintained the expression levels of these genes at a young-like level. Middle-aged players showed lower levels of IL1B than the non-physically active groups. However, there was a tendency towards a decrease in trophic and transduction factors in middle-aged groups as compared to the young controls. A statistical study of Spearman's correlations supported a positive effect of sporting activity on memory

show abstract

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

Cited by 114 publications

References 47 publications

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Peripheral Maintenance of the Axis SIRT1-SIRT3 at Youth Level May Contribute to Brain Resilience in Middle-Aged Amateur Rugby Players

Contact Info

Product

Resources

About