scholarly journals MiR155 Affect the Cerebral Ischemic Injury by Rheb/mTOR Signaling Pathway

2021 ◽  
Author(s):  
Le Chang ◽  
Yu-Ying Xue ◽  
Xu-Rong Zhu ◽  
Ye Tian ◽  
Zhi-Qin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mtor Signaling ◽  
Transcriptional Level ◽  
Mtor Signaling Pathway ◽  
Expression Levels

Abstract Ischemic stroke remains to be a leading cause of death and disability worldwide at present. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathogenesis leading to a poor prognosis for ischemic stroke patients.Recent studies have found that miR155 may be involved in the occurrence of CIRI after stroke, but it’s role and specific mechanism are not completely clear.Therefore, this study investigated the effects of miR155 expression levels on mortality, cerebral infarction volume and neuronal apoptosis in MCAO/R rats by changing the expression level of miR155 in the ischemic penumbra (IP) region of rats. QRT-PCR and Western Blotting were used to detect the expression changes of Rheb, mTOR, 4EBP1 and S6K1 under different miR155 expression levels. The results showed that inhibition of miR155 could reduce the mortality, the volume of cerebral infarction and the number of neuronal apoptosis in MCAO/R rats.The mRNA and protein expressions of Rheb, mTOR, 4EBP1 and S6K1 were increased after inhibition of miR155, and vice versa. It suggested that inhibition the expression of miR155 could alleviate CIRI in the IP by activating Rheb/mTOR signaling at the transcriptional level. At the same time, we found that the phosphorylation level of mTOR signaling pathway were also increased after inhibition of miR155, indicating that autophagy level regulated by mTOR signaling pathway may be involved in the CIRI.

scholarly journals Aescin Protects Neuron from Ischemia-Reperfusion Injury via Regulating the PRAS40/mTOR Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xinjie Gao ◽  
Heng Yang ◽  
Jiabin Su ◽  
Weiping Xiao ◽  
Wei Ni ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intravenous Thrombolysis ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mtor Signaling Pathway

Ischemic stroke is one of the major causes of disability; widely use of endovascular thrombectomy or intravenous thrombolysis leads to more attention on ischemia-reperfusion injury (I/R injury). Aescin, a natural compound isolated from the seed of the horse chestnut, has been demonstrated anti-inflammatory and antiedematous effects previously. This study was aimed at determining whether aescin could induce protective effects against ischemia-reperfusion injury and exploring the underlying mechanisms in vitro. Primary cultured neurons were subjected to 2 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of simulated reperfusion. Aescin, which worked in a dose-dependent manner, could significantly attenuate neuronal death and reduce lactate dehydrogenase (LDH) release after OGD and simulated reperfusion. Aescin treatment at a concentration of 50 μg/ml provided protection with fewer side effects. Results showed that aescin upregulated the phosphorylation level of PRAS40 and proteins in the mTOR signaling pathway, including S6K and 4E-BP1. However, PRAS40 knockdown or rapamycin treatment was able to undermine and even abolish the protective effects of aescin; meanwhile, the levels of phosphorylation PRAS40 and proteins in the mTOR signaling pathway were obviously decreased. Hence, our study demonstrated that aescin provided neuronal protective effects against I/R injury through the PRAS40/mTOR signaling pathway in vitro. These results might contribute to the potential clinical application of aescin and provide a therapeutic target on subsequent cerebral I/R injury.

scholarly journals Osthole prevents cerebral ischemia–reperfusion injury via the Notch signaling pathway

2017 ◽  
Vol 95 (4) ◽  
pp. 459-467 ◽  
Author(s):  
Junhong Guan ◽  
Xiangtai Wei ◽  
Shengtao Qu ◽  
Tao Lv ◽  
Qiang Fu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Notch 1 ◽  
Dose Dependent

Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia–reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke.

scholarly journals Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Linan Gong ◽  
Zanzan Wang ◽  
Zhenggui Wang ◽  
Zhiguo Zhang
Keyword(s):  
Er Stress ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Regulatory Relationship ◽  
Alcoholic Fatty Liver

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

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