Lin28a attenuates cerebral ischemia/reperfusion injury through regulating Sirt3-induced autophagy

Chen, Donghai; Kuang, Zheng; Wu, Henggang; Zhang, Xuchun; Ye, Wang-Yang; Tan, Xianxi; Xiong, Ye

doi:10.1016/j.brainresbull.2021.01.022

Cited by 22 publications

(17 citation statements)

References 31 publications

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“…Basal autophagic activity exists in cells under physiological conditions, while the process turns more active induced by various stress events including CIRI and plays complex roles ( Wirawan et al, 2012 ). Some studies demonstrated that the activation of autophagy ameliorated CIRI ( Sun et al, 2020b ; Xu et al, 2020 ; Zhang B. et al, 2020 ; Chen et al, 2021 ; Jin et al, 2021 ; Yihao et al, 2021 ; Zha et al, 2021 ), while more research supported that the inhibition of autophagy activation exerted a neuroprotective effect in brain stroke ( Sun et al, 2020a ; Zhang et al, 2020b ; Li and Huang, 2020 ; Mei et al, 2020 ; Shi et al, 2020 ; Wang L. et al, 2020 ; Gu et al, 2021 ; Liu N. et al, 2021 ; Shao et al, 2021 ; Wang C. et al, 2021 ; Xu et al, 2021 ; Yao et al, 2021 ; Zhang et al, 2021 ; Zhao et al, 2021 ). Obviously, the controversial dual role of the induction of autophagy in the ischemic brain is still a hot topic in research and remains to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

Wang

Dai

et al. 2022

Front. Pharmacol.

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Stroke remains one of the leading reasons of mortality and physical disability worldwide. The treatment of cerebral ischemic stroke faces challenges, partly due to a lack of effective treatments. In this study, we demonstrated that autophagy was stimulated by transient middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R). Treatment with (−)-epigallocatechin-3-gallate (EGCG), a bioactive ingredient in green tea, was able to mitigate cerebral ischemia/reperfusion injury (CIRI), given the evidence that EGCG administration could reduce the infarct volume and protect poststroke neuronal loss in MCAO/R mice in vivo and attenuate cell loss in OGD/R-challenged HT22 cells in vitro through suppressing autophagy activity. Mechanistically, EGCG inhibited autophagy via modulating the AKT/AMPK/mTOR phosphorylation pathway both in vivo and in vitro models of stroke, which was further confirmed by the results that the administration of GSK690693, an AKT/AMPK inhibitor, and rapamycin, an inhibitor of mTOR, reversed aforementioned changes in autophagy and AKT/AMPK/mTOR signaling pathway. Overall, the application of EGCG relieved CIRI by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway.

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Section: Introductionmentioning

confidence: 99%

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

Wang

Dai

et al. 2022

Front. Pharmacol.

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“…A previous study has shown that upregulation of Lin28a alleviated ischemia-reperfusion-induced nerve injury through promoting of autophagy. 32 Silencing of Lin28a in this study reversed the neuroprotective effects of PRMT8 against OGD/ R-induced cell apoptosis, inflammation, and microglia polarization.…”

Section: ■ Results and Discussionmentioning

confidence: 57%

PRMT8 Attenuates Cerebral Ischemia/Reperfusion Injury via Modulating Microglia Activation and Polarization to Suppress Neuroinflammation by Upregulating Lin28a

Zheng

Zhang

et al. 2022

ACS Chem. Neurosci.

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Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic strokeassociated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen−glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.

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“…SIRT3 can also promote the deacetylation level of COX-1, which can improve OS after I/R (Tu et al 2019 ). In addition, the promotion of autophagy by SIRT3 mediated by the AMPK–mTOR pathway can also inhibit I/R injury, but this function is achieved by removing damaged nerve cells rather than by inhibiting OS (Chen et al 2021a , b ). However, an experiment conducted in 2016 showed that SIRT3 is activated by a currently unknown mechanism and increases the deacetylation level and activity of CerS1, CerS2, and CerS6 after cerebral ischemia–reperfusion.…”

Section: Acute Neurodegenerative Diseasesmentioning

confidence: 99%

“…The location of each type of sirtuin in the cell is not the same. SIRT2 is mainly located in the cytoplasm; SIRT1, SIRT6, and SIRT7 are mainly located in the nucleus; and SIRT3, SIRT4, and SIRT5 are mainly located in mitochondria (Chen et al 2021a , b ). As a deacetylase located in mitochondria, SIRT3 must have a relationship with mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Role of SIRT3 in neurological diseases and rehabilitation training

Liu

et al. 2022

Metab Brain Dis

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Sirtuin3 (SIRT3) is a deacetylase that plays an important role in normal physiological activities by regulating a variety of substrates. Considerable evidence has shown that the content and activity of SIRT3 are altered in neurological diseases. Furthermore, SIRT3 affects the occurrence and development of neurological diseases. In most cases, SIRT3 can inhibit clinical manifestations of neurological diseases by promoting autophagy, energy production, and stabilization of mitochondrial dynamics, and by inhibiting neuroinflammation, apoptosis, and oxidative stress (OS). However, SIRT3 may sometimes have the opposite effect. SIRT3 can promote the transfer of microglia. Microglia in some cases promote ischemic brain injury, and in some cases inhibit ischemic brain injury. Moreover, SIRT3 can promote the accumulation of ceramide, which can worsen the damage caused by cerebral ischemia–reperfusion (I/R). This review comprehensively summarizes the different roles and related mechanisms of SIRT3 in neurological diseases. Moreover, to provide more ideas for the prognosis of neurological diseases, we summarize several SIRT3-mediated rehabilitation training methods.

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Lin28a attenuates cerebral ischemia/reperfusion injury through regulating Sirt3-induced autophagy

Cited by 22 publications

References 31 publications

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

PRMT8 Attenuates Cerebral Ischemia/Reperfusion Injury via Modulating Microglia Activation and Polarization to Suppress Neuroinflammation by Upregulating Lin28a

Role of SIRT3 in neurological diseases and rehabilitation training

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