TIGAR alleviates ischemia/reperfusion-induced autophagy and ischemic brain injury

Zhang, Dingmei; Zhang, Tian; Wang, Mingming; Wang, Xinxin; Qin, Yuanyuan; Wu, Junchao; Han, Rong; Sheng, Rui; Wang, Yan; Chen, Zhong; Han, Feng; Ding, Yu‐Qiang; Li, Mei; Qin, Zheng‐Hong

doi:10.1016/j.freeradbiomed.2019.04.002

Cited by 80 publications

(59 citation statements)

References 40 publications

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“…In 1995, Nitatori et al firstly confirmed the occurrence of autophagy in neurocytes after cerebral ischemia using transmission electron microscopy (Nitatori et al, 1995). In recent years, mounting evidence indicates that cerebral I/R injury closely relates to autophagy (Zhang et al, 2019a). The research by Zhang et al showed that astragaloside IV treatment exerted neuroprotective effects on cerebral I/R injury via the promotion of autophagy (Zhang et al, 2019b).…”

Section: Discussionmentioning

confidence: 99%

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

et al. 2020

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Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/ reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/ P70S6K signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

et al. 2020

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“…Therefore, it is necessary to explore more effective treatments to reduce the cerebral ischemia/reperfusion (I/R) injury and promote the repair of nerve function. Cerebral I/R injury involves complex pathophysiological processes, including autophagy (Zhang D. M. et al, 2019 ), apoptosis (Chen et al, 2017 ), oxidative stress (Rana and Singh, 2018 ), pyroptosis (Zhu et al, 2019 ), ion homeostasis imbalance (Gu et al, 2019 ), and acidosis (Fan et al, 2014 ). Among them, pyroptosis has recently been discovered as a pro-inflammatory programmed cell death process that plays an important role in cerebral I/R injury (Xia et al, 2018 ; Zhu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

Zeng

Zhou

Liang

et al. 2020

Front. Cell. Neurosci.

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Background : Cerebral ischemia–reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux. Method : PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2′,7′-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3. Results : BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis. Conclusions : BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

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“…Autophagy is an essential process in the maintenance of cellular homeostasis ( Klionsky et al, 2016 ; Levine and Kroemer, 2019 ), but it can also be rapidly induced in response to variations in the internal and external state of the cell, such as during starvation, hypoxia, accumulation of metabolites, or damage to organelles. Many neurological diseases involve alterations in autophagy ( Levine and Kroemer, 2008 ; Moloudizargari et al, 2017 ), and a large body of research indicates that autophagy is invoked during cerebral ischemia-reperfusion injury ( Zhang X. et al, 2013 ; Li et al, 2014 ; Zhang et al, 2019 ). Promoting autophagy during brain reperfusion may also contribute to mitophagy-related mitochondrial clearance and the suppression of cellular apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

Jiang

et al. 2020

Front. Cell Dev. Biol.

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Background Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than trans- differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO). Methods To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an in vitro model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used. Results Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and in vitro experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress. Conclusion We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.

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TIGAR alleviates ischemia/reperfusion-induced autophagy and ischemic brain injury

Cited by 80 publications

References 40 publications

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

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