Methylene blue attenuates neuroinflammation after subarachnoid hemorrhage in rats through the Akt/GSK-3β/MEF2D signaling pathway

Xu, Hangzhe; Li, Jianru; Wang, Zhijiang; Feng, Ma-Jing; Shen, Yong-Feng; Cao, Shenglong; Li, Tao; Peng, Yucong; Fan, Linfeng; Chen, Jingyin; Gu, Chi; Yan, Feng; Wang, Lin; Chen, Gao

doi:10.1016/j.bbi.2017.04.020

Cited by 59 publications

(59 citation statements)

References 65 publications

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“…BCL-2 family pro-apoptotic member, to oppose apoptosis (39,40). GSK-3β is a well-identified inhibitory target of Akt which plays a key role in the promotion of apoptosis (41,42). In the present study, our results showed that a notable decrease in Akt activation and consequently enhanced GSK-3β signaling were found in HFD-treated mouse livers.…”

Section: Discussionsupporting

confidence: 61%

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Su¹,

Zhang²,

Chen³

et al. 2020

Food & Nutrition Research

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Background: Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated. Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects. Design: Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) and Sirt1 siRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathways in vivo and in vitro. Results: Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27 ± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NAD + level in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover, Sirt1 knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers. Conclusion: PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1-dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.

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Section: Discussionsupporting

confidence: 61%

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Su¹,

Zhang²,

Chen³

et al. 2020

Food & Nutrition Research

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“…The phosphorylation of GSK-3β at Ser9, which indicates an inactive status, enables cells to resist various pathophysiological injuries [45]. In the CNS, GSK-3β was reported to affect the microglial activation by modulating a cascade of signals [46][47][48][49]. Thus, we employed a GSK-3β inhibitor at Ser9, TDZD, and found that both SPC and TDZD elicited a neuroprotective effect by improving M2 marker gene expression and reducing M1 marker mRNA expression [50,51].…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane preconditioning reduces brain inflammation after experimental stroke by enhancing glycogen synthesis kinase-3 β/ nuclear factor erythroid 2-related factor - dependent microglial M2 polarization

Cai

Sun²,

Wang³

et al. 2019

Preprint

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Background: Sevoflurane preconditioning (SPC) results in cerebral ischemic tolerance; however, the mechanism remains unclear. In current study, we aimed to assess the M1/M2 shift in the brain induced by SPC and whether glycogen synthesis kinase-3β (GSK-3β)-regulated nuclear factor erythroid 2-related factor (Nrf2) activation was involved in the M2 polarization mediated by SPC. Methods: Mouse primary microglia with SPC were challenged by oxygen-glucose deprivation (OGD) or lipopolysaccharide (LPS), and mice with SPC were subjected to middle cerebral artery occlusion (MCAO). Then, the mRNA and protein levels of proinflammatory/anti-inflammatory factors were analysed. GSK-3β phosphorylation and Nrf2 nuclear translocation were measured. The mRNA and protein expression of proinflammatory/anti-inflammatory factors, neurological scores, infarct volume, cellular apoptosis, the proportion of M1/M2-positive cells, and the generation of super-oxidants were examined after SPC or GSK-3β inhibitor TDZD treatment with or without Nrf2 deficiency. Results: SPC promoted M2 phenotype polarization both in vitro and in vivo . GSK-3β phosphorylation at Ser9 was increased after SPC. Both SPC and TDZD administration enhanced Nrf2 nuclear translocation, promoted M2 phenotype polarization and elicited a neuroprotective effect. Nrf2 deficiency abolished the promoted M2 polarization and ischemic tolerance induced by TDZD treatment. The reduced percentage of M1-positive cells and super-oxidants generation induced by SFC or TDZD was also reversed by Nrf2 knockdown. Conclusions: Our results indicated that SPC exerts brain ischemic tolerance and enhances M2 polarization by GSK-3β-dependent Nrf2 activation, which provides a novel mechanism for SPC-induced neuroprotection.

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“…It is essential in energy metabolism (Martin et al, 2018) and nerve cell development (Chen et al, 2019a). The levels of GSK3β can be decreased by phosphorylation at the ser9 site (Xu et al, 2017;Chen et al, 2019b). Additionally, GSK3β (Ser9) can be phosphorylated by Akt, inhibiting its enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Zeng

Bai

Jiang

et al. 2020

Front. Cell. Neurosci.

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Neonatal hypoxic-ischemic (HI) brain injury is a detrimental disease, which results in high mortality and long-term neurological deficits. Nevertheless, the treatment options for this disease are limited. Thus, the aim of the present study was to assess the role of liraglutide in neonatal HI brain injury in rats and investigate the associated mechanisms. The results showed that treatment with liraglutide significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Moreover, treatment with liraglutide inhibited apoptosis and promoted neuronal survival both in the rat model and following oxygen-glucose deprivation (OGD) insult. LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), partially reversed these therapeutic effects, suggesting that the PI3K/protein kinase B (Akt) pathway was involved. In conclusion, our data revealed that treatment with liraglutide exerts neuroprotection after neonatal HI brain injury via the PI3K/Akt/glycogen synthase kinase-3β (GSK3β) pathway and may be a promising therapy for this disease.

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Methylene blue attenuates neuroinflammation after subarachnoid hemorrhage in rats through the Akt/GSK-3β/MEF2D signaling pathway

Cited by 59 publications

References 65 publications

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice

Sevoflurane preconditioning reduces brain inflammation after experimental stroke by enhancing glycogen synthesis kinase-3 β/ nuclear factor erythroid 2-related factor - dependent microglial M2 polarization

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

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