Resveratrol Protects HUVECs from Oxidized-LDL Induced Oxidative Damage by Autophagy Upregulation via the AMPK/SIRT1 Pathway

Guo, Hualei; Chen, Yanling; Liao, Lingjie; Wu, Weikang

doi:10.1007/s10557-013-6442-4

Cited by 96 publications

(70 citation statements)

References 25 publications

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“…We found that low concentrations of TNF-α increased SIRT1 expression and induced autophagy, and SIRT1 activator RSV augmented the autophagy of VAFs induced by TNF-α. Studies have shown that RSV upregulated SIRT1 expression and triggered the stimulatory response of shear stress or ox-LDL on cell autophagy in VECs [5, 26]. Furthermore, we found that SIRT1 inhibition by sirtinol or SIRT1 knockdown attenuated cell autophagy in VAFs stimulated with TNF-α.…”

Section: Discussionsupporting

confidence: 58%

SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway

Wang

Jing

et al. 2017

Cell Physiol Biochem

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Background/Aims: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs). Methods: Cell autophagy was evaluated by fluorescence microscope and transmission electron microscopy. The expression of protein and mRNA were determined by Western blot analysis and real time-PCR. The production of cytokine was detected by ELISA. Results: TNF-α induced autophagy and increased SIRT1 expression in VAFs. SIRT1 activator resveratrol enhanced TNF-α-induced VAF autophagy. In contrast, SIRT1 knockdown attenuated VAF autophagy. Both the Akt inhibitor MK2206 and mTOR inhibitor rapamycin further increased TNF-α-induced VAF autophagy. Furthermore, SIRT1 knockdown increased Akt phosphorylation and inhibited the autophagy in VAFs. However, MK2206 attenuated the effect of SIRT1 knockdown on VAF autophagy. In addition, ingenuity pathway analysis showed that there is a relationship between cell autophagy and inflammation. We found that SIRT1 knockdown increased the expression of NLRP3 and interleukin (IL)-6 and promoted the production of IL-1β in VAFs. Further study showed that autophagy activation decreased the expression of NLRP3 and IL-6 and inhibited the production of IL-1β, whereas autophagy inhibition increased the inflammatory response of VAFs. More importantly, our study showed that autophagy was involved in the degradation of NLRP3 through the autophagy-lysosome pathway. Conclusion: SIRT1 not only regulates VAF autophagy through the Akt/mTOR signaling pathway but also suppresses the inflammatory response of VAFs through autophagy.

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Section: Discussionsupporting

confidence: 58%

SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway

Wang

Jing

et al. 2017

Cell Physiol Biochem

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“…The AMPK/NADPH-oxidase/Akt/eNOS signaling pathway is also modulated by quercetin, an antioxidant that activates SIRT1 and suppresses the endothelial oxidative injuries induced by oxidized-low density lipoproteins (oxLDL) (76). Similar to quercetin, resveratrol attenuates vascular endothelial inflammation and oxLDL-induced injury by upregulating the AMPK/SIRT1 or CAMP-PRKA-AMPK-SIRT1 signaling pathways (34,61,81,138). In particular, oxLDL inhibits the autophagic flux through a mechanism involving the oxLDL-induced SIRT1-dependent lysosomal dysfunction (216,217).…”

Section: Sirt1 and Atherosclerosismentioning

confidence: 99%

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

293

238

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Significance: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD + )-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. Critical Issues: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. Future Directions: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple ''omic'' technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

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“…For example, sheer stress induces SIRT1, AMPK, eNOS, and mitochondrial biogenesis , and this is associated with phosphorylation and stabilization of SIRT1 by calmodulin-dependent protein kinase kinase (Wen et al 2013). Inhibition of this SIRT1 induction sensitizes ECs to damage inflicted by oxidized LDL (Guo et al 2013) and sensitizes apoE À/À mice to atherosclerosis (Zhang et al 2008). The SIRT1/AMPK axis in ECs has been shown to be inducible by exercise or resveratrol in mice (Cacicedo et al 2011;Takizawa et al 2013).…”

Section: Endothelium and Smooth Musclementioning

confidence: 99%

Calorie restriction and sirtuins revisited

2013

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Calorie or dietary restriction (CR) has attracted attention because it is the oldest and most robust way to extend rodent life span. The idea that the nutrient sensors, termed sirtuins, might mediate effects of CR was proposed 13 years ago and has been challenged in the intervening years. This review addresses these challenges and draws from a great body of new data in the sirtuin field that shows a systematic redirection of mammalian physiology in response to diet by sirtuins. The prospects for drugs that can deliver at least a subset of the benefits of CR seems very real.

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Resveratrol Protects HUVECs from Oxidized-LDL Induced Oxidative Damage by Autophagy Upregulation via the AMPK/SIRT1 Pathway

Abstract: Resveratrol protected HUVECs from oxidative damage caused by ox-LDL. This effect was mediated by Sirt1-dependent autophagy via the AMPK/ Sirt1 pathway.

Cited by 96 publications

References 25 publications

SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway

SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

Calorie restriction and sirtuins revisited

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