scholarly journals GW29-e0760 Tanshinone IIA protects H9c2 cells from reactive oxygen species through inhabiting excessive autophagy via activation of PI3K/Akt/mTOR signaling pathway

2018 ◽  
Vol 72 (16) ◽  
pp. C24
Author(s):  
Xiaoping Wang ◽  
Mingyan Shao ◽  
Yong Wang
2021 ◽  
Vol 12 ◽  
Author(s):  
Yucong Xue ◽  
Muqing Zhang ◽  
Miaomiao Liu ◽  
Yu Liu ◽  
Li Li ◽  
...  

8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.


Nanomedicine ◽  
2020 ◽  
Vol 15 (14) ◽  
pp. 1419-1435
Author(s):  
Lu Jia ◽  
Shuang-Li Hao ◽  
Wan-Xi Yang

Due to their unique physicochemical properties, nanoparticles (NPs) have been increasingly developed for use in various fields. However, there has been both growing negative concerns with toxicity and positive realization of opportunities in nanomedicine, coming from the growing understanding of the associations between NPs and the human body, particularly relating to their cellular autophagic effects. This review summarizes NP-induced autophagy via the modulation of the mTOR signaling pathway and other associated signals including AMPK and ERK and also demonstrates how reactive oxygen species generation greatly underlies the regulation processes. The perspectives in this review aim to contribute to NP design, particularly in consideration of nanotoxicity and the potential for the precise application of NPs in nanomedicine.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
V. Jaenen ◽  
S. Fraguas ◽  
K. Bijnens ◽  
M. Heleven ◽  
T. Artois ◽  
...  

AbstractDespite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically H2O2, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or H2O2 have the potential to rescue regeneration after MEK-inhibition, either by H2O2-treatment or light therapy, (2) ROS and/or H2O2 are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.


Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 047-057
Author(s):  
Lei Gong ◽  
Xuyang Wang ◽  
Jinyu Pan ◽  
Mingjun Zhang ◽  
Dian Liu ◽  
...  

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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