Neuroprotective effect of ginkgetin in experimental cerebral ischemia/reperfusion via apoptosis inhibition and PI3K/Akt/mTOR signaling pathway activation

2019 ◽  
Vol 120 (10) ◽  
pp. 18487-18495 ◽  
Author(s):  
Zhaohua Tian ◽  
Congyao Tang ◽  
Zhigang Wang
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Cerebral Ischemia Reperfusion ◽  
Apoptosis Inhibition ◽  
Pathway Activation ◽  
Experimental Cerebral Ischemia

scholarly journals Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Zhao ◽  
Huanming Li ◽  
Qian Gao ◽  
Jin Xu ◽  
Yongjie Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Penumbra ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats (p < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment (p < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein (p < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.

scholarly journals The role of autophagy in the thyroid tumors development, connection with the AKT/m-TOR signaling pathway activation

2020 ◽  
Vol 15 (3) ◽  
pp. 110-117
Author(s):  
Liudmila V. Spirina ◽  
Sventlana Yu. Chizhevskaya ◽  
Irina V. Kondakova ◽  
Nataliya V. Tarasenko
Keyword(s):  
Thyroid Cancer ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Tor Signaling ◽  
Resistance To Treatment ◽  
Development Of Resistance ◽  
Apoptosis Inhibition ◽  
Pathway Activation ◽  
Intracellular Process

Autophagy is an important intracellular process that supports cell death and survival. Oncogenesis is associated with a change in the AKT/mTOR signaling pathway status. At the same time, the existence of protective autophagy, as one of the mechanisms of disease progression and the formation of resistance to treatment, has been proven. The review describes the significant mechanisms of the autophagy development, its association with AKT/mTOR signaling pathway. A molecule mTOR in TORC1 complex is associated with the oncogenesis, it provides the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The participation of this phenomenon at all stages of carcinogenesis, influencing on the main signal kinases: AKT, mTOR, is noted. It is shown that in most cases this mechanism is responsible for the progression of the disease and the development of resistance to treatment. The development of thyroid cancer associated with the BRAF mutation and with the activation of the RET oncoprotein, as well as with the formation of radio-resistant forms of the disease is associated with molecular peculiarities of autophagy. Given the inconsistency of this phenomenon regarding their influence on the processes of oncogenesis, its role in the development of thyroid cancer is still unknown.

scholarly journals The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 047-057
Author(s):  
Lei Gong ◽  
Xuyang Wang ◽  
Jinyu Pan ◽  
Mingjun Zhang ◽  
Dian Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Mtor Signaling ◽  
Maximal Rate ◽  
H9c2 Cells ◽  
Mtor Signaling Pathway ◽  
Cardioprotective Effects

AbstractObjectiveThe purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism.MethodsSprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.ResultsIn vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dtmax), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dtmax) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.ConclusionThe combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

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