Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK

Guo, Shuang; Yao, Qing; Ke, Zhiqiang; Chen, Hongguang; Wu, Jiliang; Liu, Chao

doi:10.1016/j.mce.2015.05.034

Cited by 103 publications

(79 citation statements)

References 41 publications

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“…AMPK, a major cellular energy sensor and a master regulator of metabolic homeostasis, plays an important role in regulating CM apoptosis and is an essential component of the adaptive response to CM stress (Zhang et al 2009; Zhuo et al 2013; Guo et al 2015; Qi and Young 2015). To investigate whether nicotine-plus-HFD-induced CM apoptosis is associated with the inactivation of AMPK, we compared the in vivo expression of ventricular phospho-AMPK in various treatment groups (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidative stress has been implicated in apoptotic signaling in various cell types, including cardiomyocytes (Zhou et al 2010; Sinha-Hikim et al 2011a; Guo et al 2015; Sun et al 2006). Consistent with the role of oxidative stress in CM apoptosis, we found, in the present study, that the combined treatment of nicotine plus HFD generates greater oxidative stress, as evidenced by increase ventricular 4-HNE expression compared with either treatment alone.…”

Section: Discussionmentioning

confidence: 99%

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Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis

et al. 2016

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Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0.75 mg/kg body weight [BW]) or saline for 16 weeks. An additional group of nicotine-treated mice on HFD received twice-daily IP injections of mecamylamine (1 mg/kg BW), a non-selective nicotinic acetylcholine receptor antagonist, for 16 weeks. Nicotine when combined with HFD led to a massive increase in CM apoptosis that was fully prevented by mecamylamine treatment. Induction of CM apoptosis was associated with increased oxidative stress and activation of caspase-2-mediated intrinsic pathway signaling coupled with inactivation of AMP-activated protein kinase (AMPK). Furthermore, nicotine treatment significantly (P < 0.05) attenuated the HFD-induced decrease in fibroblast growth factor 21 (FGF21) and silent information regulator 1 (SIRT1). We conclude that nicotine, when combined with HFD, triggers CM apoptosis through the generation of oxidative stress and inactivation of AMPK together with the activation of caspase-2-mediated intrinsic apoptotic signaling independently of FGF21 and SIRT1.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis

et al. 2016

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“…However, the therapeutic potential of resveratrol and other polyphenolic compounds as anti-diabetic drugs has been controversial because of non-SirT1-mediated actions 37, 38 . Several small molecule activators of SirT1 have been developed, which exert more specific and/or potent effects on SirT1 than resveratrol 24 , and are currently in clinical trials for type 2 diabetes and metabolic disorders (ClinicalTrials.gov identifier NCT01018628).…”

Section: Discussionmentioning

confidence: 99%

Vascular Smooth Muscle Sirtuin-1 Protects Against Diet-Induced Aortic Stiffness

et al. 2016

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Arterial stiffness, a major cardiovascular risk factor, develops within two months in mice fed a high fat, high sucrose diet (HFHS), serving as a model of human metabolic syndrome, and is associated with activation of pro-inflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD+-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity (PWV), in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM specific (SMTG) genetic SirT1 over-expression prevented PWV increases induced by HFHS feeding, over 8 months. Administration of resveratrol or S17834, two polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 over-expression (SirBACO), without evident metabolic improvements. Additionally, HFHS-induced PWV increases were reversed by one-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in NFκB activation and VCAM-1 and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and anti-oxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome.

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“…Recent advances show that resveratrol regulates autophagy in cardiovascular disorders [13]. We previously reported that resveratrol attenuated high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK signaling [14]. In the present study, we sought to investigate the ability of resveratrol to modulate autophagy and apoptosis in cardiac cells under diabetic conditions.…”

Section: Introductionmentioning

confidence: 98%

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. Methods: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). Results: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1–Bcl-2 complex. Conclusion: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.

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Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK

Cited by 103 publications

References 41 publications

Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis

Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis

Vascular Smooth Muscle Sirtuin-1 Protects Against Diet-Induced Aortic Stiffness

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

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