Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway

Zhao, Haosen; Chen, Shurui; Gao, Kai; Zhou, Zipeng; Wang, Chen; Shen, Zhaoliang; Guo, Yuanqiang; Li, Zhuo; Wan, Zhanghui; Liu, Chang; Mei, Xifan

doi:10.1016/j.neuroscience.2017.02.027

Cited by 164 publications

(106 citation statements)

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“…It has been reported that two SIRT1 activators, resveratrol and SRTAW04, mediate oxidative stress‐induced autophagy, indicating that SIRT1 and activation of autophagy form an essential protective mechanism for cell survival . Resveratrol, a SIRT1 activator, elevates the expression of Beclin‐1 and LC3 and inhibits the expression of apoptotic proteins . Previous evidence also suggested that MY induces autophagic clearance of tau to reduce the formation of neurofibrillary tangles .…”

Section: Discussionmentioning

confidence: 99%

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

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Background Muscle atrophy and weakness are adverse effects of high dose or the sustained usage of glucocorticoids. Loss of mitochondria and degradation of protein are highly correlated with muscle dysfunction. The deacetylase sirtuin 1 (SIRT1) plays a vital role in muscle remodelling. The current study was designed to identify myricanol as a SIRT1 activator, which could protect skeletal muscle against dexamethasone‐induced wasting. Methods The dexamethasone‐induced atrophy in C2C12 myotubes was evaluated by expression of myosin heavy chain, muscle atrophy F‐box (atrogin‐1), and muscle ring finger 1 (MuRF1), using western blots. The mitochondrial content and oxygen consumption were assessed by MitoTracker staining and extracellular flux analysis, respectively. Muscle dysfunction was established in male C57BL/6 mice (8–10 weeks old, n = 6) treated with a relatively high dose of dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, forced swimming capacity, muscle weight, and muscle histology were assessed. The expression of proteolysis‐related, autophagy‐related, apoptosis‐related, and mitochondria‐related proteins was analysed by western blots or immunoprecipitation. Results Myricanol (10 μM) was found to rescue dexamethasone‐induced muscle atrophy and dysfunction in C2C12 myotubes, indicated by increased expression of myosin heavy chain (0.33 ± 0.14 vs. 0.89 ± 0.21, * P < 0.05), decreased expression of atrogin‐1 (2.31 ± 0.67 vs. 1.53 ± 0.25, * P < 0.05) and MuRF1 (1.55 ± 0.08 vs. 0.99 ± 0.12, ** P < 0.01), and elevated ATP production (3.83 ± 0.46 vs. 5.84 ± 0.79 nM/mg protein, ** P < 0.01), mitochondrial content (68.12 ± 10.07% vs. 116.38 ± 5.12%, * P < 0.05), and mitochondrial oxygen consumption (166.59 ± 22.89 vs. 223.77 ± 22.59 pmol/min, ** P < 0.01). Myricanol directly binds and activates SIRT1, with binding energy of −5.87 kcal/mol. Through activating SIRT1 deacetylation, myricanol inhibits forkhead box O 3a transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, and increases peroxisome proliferator‐activated receptor γ coactivator‐1α activity to promote mitochondrial biogenesis. In dexamethasone‐induced muscle wasting C57BL/6 mice, 5 mg/kg myricanol treatment reduces the loss of muscle mass; the percentages of quadriceps and gastrocnemius muscle in myricanol‐treated mice are 1.36 ± 0.02% and 0.87 ± 0.08%, respectively (cf. 1.18 ± 0.06% and 0.78 ± 0.05% in dexamethasone‐treated mice, respectively). Myricanol also rescues dexamethasone‐induced muscle weakness, indicated by improved grip strength (70.90 ± 4.59 vs. 120.58 ± 7.93 g, ** P < 0.01) and prolonged swimming exhaustive time (48.80 ± 11.43 vs. 83.75 ± 15.19 s, **...

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Section: Discussionmentioning

confidence: 99%

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

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“…Emerging studies have shown that SIRT1 exhibits promising therapeutic effects for the treatment of CVDs (Miranda et al, ; Winnik, Auwerx, Sinclair, & Matter, ). Recently, SIRT1/AMPK has been an accepted target for small molecule screening, such as resverotral (Zhao et al, ) and botulin (Bai et al, ). The PI3K/Akt signaling pathway is considered as an important role in cell survival and metabolism, particularly in the regulation of endothelial apoptosis (Luo, Sun, et al, ).…”

Section: Introductionmentioning

confidence: 99%

SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high‐fat diet‐induced atherosclerosis in ApoE−/− mice

Luo

et al. 2019

Phytotherapy Research

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Total aralosides of Aralia elata (Miq) Seem (TASAESs) possess multiple pharmacological activity, such as anti‐inflammation, antioxidation, and antiapoptosis. However, there is no literature reporting the antiatherosclerotic effect and mechanism of TASAES so far. The aim of this study was to investigate the antiatherosclerotic effects in high‐fat diet‐induced ApoE−/− mice and potential mechanism of TASAES in ox‐LDL‐injured endothelial cells. In vivo assay, our data demonstrated that TASAES significantly reduced the atherosclerotic plaque size and caspase‐3 expression level in aortic valve. In vitro, we found that TASAES could increase endothelial cell viability, attenuated mitochondrial membrane potential depolarization, and endothelial cells apoptosis. In addition, we found that TASAES could activate SIRT1/AMPK and Akt/eNOS signaling pathways. Importantly, EX527, SIRT1 siRNA, and LY294002, Akt siRNA, remarkably abolished the antiapoptotic effects of TASAES. In conclusion, this study demonstrated that SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of TASAES against atherosclerotic mice, suggesting that TASAES is a candidate drug for atherosclerosis treatment.

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“…Interestingly, autophagy plays an important role in the repair of nerve function in the CNS [8][9][10]. Moreover, we found that levels of autophagy are significantly increased after SCI, and that neuronal autophagy is associated with neurological function recovery as well as inhibition of apoptosis in the spinal cord [11]. Apoptosis plays an essential role during animal recovery after injury [12].…”

Section: Introductionmentioning

confidence: 78%

“…Moreover, we showed that it inhibited the apoptotic potential of neurons induced by SCI [11,33,34]. The regulation of autophagy is very complex and includes many signaling pathways and players, such as P53, P62, Bcl-2, UVRAG, and Beclin-1.…”

Section: Biological and Pharmaceutical Bulletin Advance Publicationmentioning

confidence: 98%

Triggering of Autophagy by Baicalein in Response to Apoptosis after Spinal Cord Injury: Possible Involvement of the PI3K Activation

Li¹,

Lin²,

Xu³

et al. 2018

Biological & Pharmaceutical Bulletin

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Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway

Cited by 164 publications

References 40 publications

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high‐fat diet‐induced atherosclerosis in ApoE−/− mice

Triggering of Autophagy by Baicalein in Response to Apoptosis after Spinal Cord Injury: Possible Involvement of the PI3K Activation

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