Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB

Zhou, Xi; Yang, Jining; Zhou, Min; Zhang, Yu; Yang, Liu; Hou, Pengfei; Zeng, Xianglong; Lv, Yi; Mi, Mantian

doi:10.1186/s12986-019-0371-6

Cited by 61 publications

(38 citation statements)

References 49 publications

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“…Emerging evidence indicates that RESV attenuates endothelial oxidative injury in HUVECs by inducing autophagy [11,23]. Here, in the present study we found that blocking autophagy with 3-MA aggravated the apoptosis by upregulating caspase3 expression, while inducing autophagy with rapamycin relieved the apoptosis, indicating that autophagy confers the ability to protect endothelial cells from CSE-induced apoptosis.…”

Section: Discussionsupporting

confidence: 67%

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

Zong

Liu

et al. 2020

Preprint

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Background: Increasing evidences have showed that endothelial apoptosis contributes to cigarette smoke (CS)-induced disease progression, such as chronic obstructive pulmonary disease (COPD). Our previous studies have validated Notch1 as an anti-apoptotic signaling in cigarette smoke (CS)-induced endothelial apoptosis. Resveratrol (RESV) is a naturally occurring polyphenol that exhibits an anti-apoptotic activity in endothelial cells that exposed to many kinds of destructive stimulus. However, the effects of resveratrol on Notch1 signaling in CS-induced endothelial apoptosis have not yet been fully elucidated. Therefore, the aim of this study was to examine whether RESV can protect endothelial cells from cigarette smoke induced apoptosis via regulating Notch1 signaling. Methods: Human umbilical vein endothelial cells (HUVECs) were pretreated with RESV for 2 h, followed by cotreatment with 2.5%CSE for 24h to explore the role of RESV in CSE induced endothelial apoptosis. 3-methyladenine (3-MA) or rapamycin was used to alter autophagic levels. Lentivirus Notch1 intracellular domain (LV-N1ICD) or γ-secretase inhibitor (DAPT) were used to change Notch1 expression. The expression of Notch1, autophagic and apoptotic markers were examined by Western blot and the apoptosis rate was detected by Flow cytometry analysis. Results: Our results showed that activating autophagy reduced CSE-induced endothelial apoptosis, while blocking autophagy promoted cell apoptosis in HUVECs. RESV pretreatment attenuated the CSE-induced endothelial apoptosis and activated Notch1 signaling. RESV pretreatment also increased LC3b-II and Beclin1 production, decreased p62 and mTOR expression. 3-MA treatment inhibited autophagy and aggravated CSE induced apoptosis, while rapamycin promoted autophagy, led to a decrease in cell apoptosis. LV-N1ICD transfection upregulated autophagy and reduced apoptosis. However, this protective effect was abolished by 3-MA treatment. In cells treated with DAPT, autophagy was decreased, while apoptosis was increased. RESV partly rescued the DAPT induced apoptosis by activating Notch1 signaling. Conclusion: In HUVECs, RESV attenuates CSE induced endothelial apoptosis by inducing autophagy in a Notch1-dependent manner.

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Section: Discussionsupporting

confidence: 67%

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

Zong

Liu

et al. 2020

Preprint

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“…Reducing the ischemia-reperfusion injury-induced oxidative stress by inhibiting the activation of p38 MAPK pathway to increase antioxidants like GSH and scavenge free radicals [28] In vivo Rats 5, 10 mg/kg Activating SIRT1 to scavenge ROS [29] In vivo Mice 15, 30, 60 mg/kg Activating AMPK, SIRT1, and Nrf2 associated antioxidant defense pathways to improve systemic oxidative and nitrosative stress [30] In vivo Sows 300 mg/kg Regulating antioxidant gene expression via Keap1/Nrf2 pathway and SIRT1 [31] In vitro HUVECs 10 µM Inducing autophagy via the activation of TFEB [32] In vitro HEK293 cells or HEK293T 5 µg/mL Inducing autophagy via the AMPK-mediated inhibition of mTOR signaling [33] Anti-inflammatory activities…”

Section: µMmentioning

confidence: 99%

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

Meng

Zhou

Zhao

et al. 2020

Foods

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Resveratrol is a bioactive compound in many foods. Since its anticancer activity was reported in 1997, its health benefits have been intensively investigated. Resveratrol has antioxidant, anti-inflammatory, immunomodulatory, glucose and lipid regulatory, neuroprotective, and cardiovascular protective effects, therefore, can protect against diverse chronic diseases, such as cardiovascular diseases (CVDs), cancer, liver diseases, obesity, diabetes, Alzheimer's disease, and Parkinson's disease. This review summarizes the main findings of resveratrol-related health benefits in recent epidemiological surveys, experimental studies, and clinical trials, highlighting its related molecular mechanisms. Resveratrol, therefore, has been regarded as a potent candidate for the development of nutraceuticals and pharmaceuticals to prevent and treat certain chronic diseases. Foods 2020, 9, 340 Iranian (Tehranian)/Iran Cross-sectional study, part of the TLG study N = 2618 (male, 1162; female, 1456) Quartiles: Q1: 0.014 mg/day Q2: 0.015-0.027 mg/day Q3: 0.028-0.053 mg/day Q4: 0.054 mg/day (FFQ on a daily frequency, 1 year prior) Null: Significantly associated with WC, TG, HDL, BG, and MS Unfavorable: The top quantile of intake (0.054 mg/day and more) was positively associated with high BP (HR = 1.52; 95% CI: 1.02-2.27) [19] Spanish/Spain Cross-sectional study, part of the PREDIMED study N = 1000 (male, 479; female, 521) Quintiles: Q1: 0.48 mg/day Q2: 1.04 mg/day Q3: 2.04 mg/day Q4: 5.75 mg/day (FFQ, 1 year prior) Favorable: Significantly decreased CVD risk factors (FBG (95% CI: −1.033 to −0.033); TG (95% CI: −1.998 to −0.029); and heart rate (95% CI: −0.467 to −0.087)). Null: Resveratrol intake was not significantly associated with TC, HDL, LDL and BP [6] Spanish/Spain Cross-sectional study, part of the PREDIMED study N = 7172 (male, 3249; female, 3923) Quintiles: Q1: 0.48 mg/d Q2: 1.04 mg/d Q3: 2.04 mg/day Q4: 5.75 mg/day (FFQ, 1 year prior) Favorable: High dose intake (5.75 mg/d) significantly reduced all-cause mortality by 52% (HR = 0.48; 95% CI: 0.25-0.91) Null: No significant CVD risk reduction (HR = 0.77; 95% CI: 0.35-1.72) [21,22] Swedish/Sweden Case-control study N = 1400 (case, 594 including (OAC, 181; OSCC, 158; JAC, 255)) (control, 806) Control: 0.1 mg/day OAC: 0.07 mg/day OSCC: 0.11 mg/day JAC: 0.09 mg/day (FFQ, 20 years prior) Favorable: In a significantly negative association with the risk of 3 subtypes of esophageal cancer (OAC (95% CI: 0.12-0.49); OSCC (95% CI: 0.15-0.65), and JAC (95% CI: 0.28-0.84)) [5] Italian/Italy Cohort study, "Aging in the Chianti Region" N = 529 (male, 236; female, 293) Tertiles: T1: 0.1 mg/day T2: 0.1-1.1 mg/day T3: >1.1 mg/day (FFQ) Favorable: Inversely associated with the risk of frailty syndrome during the first 3-year follow-up (T3 vs. T1: OR = 0.11; 95% CI: 0.03-0.45) Null: No substantial association with (i) risk of frailty syndrome in 6-, or 9-year follow-up; (ii) inflammatory biomarkers including IL-6, IL-1β, TNF-α, and CRP; (iii) CVD, cancer or all-cause mortality [18] Chinese/Chin...

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“…Autophagy is an essential intracellular process responsible for the selective degradation of pathogens, damaged organelles and proteins that cannot be degraded by the proteasome, to support protein and organellar homeostasis, as well as recycling of biomolecular resources, to maintain energy homeostasis and cell survival [23]. Emerging evidence indicates that RESV attenuates endothelial oxidative injury in HUVECs by inducing autophagy [13,24]. Here, in the present study we found that blocking autophagy with 3-MA aggravated the apoptosis by upregulating caspase3 expression, while inducing autophagy with rapamycin relieved the apoptosis, indicating that autophagy confers the ability to protect endothelial cells from CSE-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

Zong

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Endothelial apoptosis contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Our previous studies have validated Notch1 as an anti-apoptotic signaling in cigarette smoke (CS)-induced endothelial apoptosis. Resveratrol (RESV) is a naturally occurring polyphenol that exhibits an anti-apoptotic activity in endothelial cells that exposed to many kinds of destructive stimulus. However, the effects of resveratrol on Notch1 signaling in CS-induced endothelial apoptosis have not yet been fully elucidated. Therefore, the aim of this study was to examine whether RESV can protect endothelial cells from cigarette smoke induced apoptosis via regulating Notch1 signaling. Methods HUVECs were pretreated with RESV for 2 h, followed by cotreatment with 2.5%CSE for 24h to explore the role of RESV in CSE induced endothelial apoptosis. 3-MA or rapamycin was used to alter autophagic levels. Lentivirus Notch1 intracellular domain (LV-N1ICD) or γ-secretase inhibitor (DAPT) were used to change Notch1 expression. The expression of Notch1, autophagic and apoptotic markers were examined by Western blot and the apoptosis rate was detected by Flow cytometry analysis. Results Our results showed that activating autophagy reduced CSE-induced endothelial apoptosis, while blocking autophagy promoted cell apoptosis in HUVECs. RESV pretreatment attenuated the CSE-induced endothelial apoptosis and activated Notch1 signaling. RESV pretreatment also increased LC3b-II and Beclin1 production, decreased p62 and mTOR expression. 3-MA treatment inhibited autophagy and aggravated CSE induced apoptosis, while rapamycin promoted autophagy, led to a decrease in cell apoptosis. LV-N1ICD transfection upregulated autophagy and reduced apoptosis. However, this protective effect was abolished by 3-MA treatment. In cells treated with DAPT, autophagy was decreased, while apoptosis was increased. RESV partly rescued the DAPT induced apoptosis by activating Notch1 signaling. Conclusion In HUVECs, RESV attenuates CSE induced endothelial apoptosis by inducing autophagy in a Notch1-dependent manner.

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Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB

Cited by 61 publications

References 49 publications

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy

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