scholarly journals MiR-21 mediates the protection of kaempferol against hypoxia/reoxygenation-induced cardiomyocyte injury via promoting Notch1/PTEN/AKT signaling pathway

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241007
Author(s):  
Jinxi Huang ◽  
Zhenhui Qi
Keyword(s):  
Signaling Pathway ◽  
Cell Injury ◽  
Akt Signaling ◽  
Flavonoid Compound ◽  
H9c2 Cell ◽  
H9c2 Cells ◽  
Akt Signaling Pathway ◽  
Down Regulation ◽  
Apoptotic Protein ◽  
Hypoxia Reoxygenation

Kaempferol, a natural flavonoid compound, possesses potent myocardial protective property in ischemia/reperfusion (I/R), but the underlying mechanism is not well understood. The present study was aimed to explore whether miR-21 contributes to the cardioprotective effect of kaempferol on hypoxia/reoxygenation (H/R)-induced H9c2 cell injury via regulating Notch/phosphatase and tensin homologue (PTEN)/Akt signaling pathway. Results revealed that kaempferol obviously attenuates H/R-induced the damages of H9c2 cells as evidence by the up-regulation of cell viability, the down-regulation of lactate dehydrogenase (LDH) activity, the reduction of apoptosis rate and pro-apoptotic protein (Bax) expression, and the increases of anti-apoptotic protein (Bcl-2) expression. In addition, kaempferol enhanced miR-21 level in H9c2 cells exposed to H/R, and inhibition of miR-21 induced by transfection with miR-21 inhibitor significantly blocked the protection of kaempferol against H/R-induced H9c2 cell injury. Furthermore, kaempferol eliminated H/R-induced oxidative stress and inflammatory response as illustrated by the decreases in reactive oxygen species generation and malondialdehyde content, the increases in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities, the decreases in pro-inflammatory cytokines interleukin (IL)-1β, IL-8 and tumor necrosis factor-alpha levels, and an increase in anti-inflammatory cytokine IL-10 level, while these effects of kaempferol were all reversed by miR-21 inhibitor. Moreover, results elicited that kaempferol remarkably blocks H/R-induced the down-regulation of Notch1 expression, the up-regulation of PTEN expression, and the reduction of P-Akt/Akt, indicating that kaempferol promotes Notch1/PTEN/AKT signaling pathway, and knockdown of Notch1/PTEN/AKT signaling pathway induced by Notch1 siRNA also abolished the protection of kaempferol against H/R-induced the damage of H9c2 cells. Notably, miR-21 inhibitor alleviated the promotion of kaempferol on Notch/PTEN/Akt signaling pathways in H9c2 cells exposed to H/R. Taken together, these above findings suggested thatmiR-21 mediates the protection of kaempferol against H/R-induced H9c2 cell injuryvia promoting Notch/PTEN/Akt signaling pathway.

scholarly journals Knockdown of Tripartite Motif 8 Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of PI3K/Akt Signaling Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972094924
Author(s):  
Xiaoyan Dang ◽  
Yong Qin ◽  
Changwei Gu ◽  
Jiangli Sun ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
H9c2 Cells ◽  
Loss Of Function ◽  
Akt Signaling Pathway ◽  
Tripartite Motif ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Tripartite motif 8 (TRIM8) is a member of the TRIM protein family that has been found to be implicated in cardiovascular disease. However, the role of TRIM8 in myocardial ischemia/reperfusion (I/R) has not been investigated. We aimed to explore the effect of TRIM8 on cardiomyocyte H9c2 cells exposed to hypoxia/reoxygenation (H/R). We found that TRIM8 expression was markedly upregulated in H9c2 cells after stimulation with H/R. Gain- and loss-of-function assays proved that TRIM8 knockdown improved cell viability of H/R-stimulated H9c2 cells. In addition, TRIM8 knockdown suppressed reactive oxygen species production and elevated the levels of superoxide dismutase and glutathione peroxidase. Knockdown of TRIM8 suppressed the caspase-3 activity, as well as caused significant increase in bcl-2 expression and decrease in bax expression. Furthermore, TRIM8 overexpression exhibited apposite effects with knockdown of TRIM8. Finally, knockdown of TRIM8 enhanced the activation of PI3K/Akt signaling pathway in H/R-stimulated H9c2 cells. Inhibition of PI3K/Akt by LY294002 reversed the effects of TRIM8 knockdown on cell viability, oxidative stress, and apoptosis of H9c2 cells. These present findings defined TRIM8 as a therapeutic target for attenuating and preventing myocardial I/R injury.

scholarly journals Nerol protects against hypoxia/reoxygenation-induced apoptotic injury by activating PI3K/AKT signaling in cardiomyocytes

STEMedicine ◽  
2021 ◽  
Vol 2 (6) ◽  
pp. e87
Author(s):  
Jin Cheng ◽  
Qing Zou ◽  
Yugang Xue
Keyword(s):  
Protein Kinase ◽  
Western Blot ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cardioprotective Effect ◽  
H9c2 Cells ◽  
Akt Signaling Pathway ◽  
Ldh Release ◽  
Hypoxia Reoxygenation

Background: Nerol was reported as a natural anti-oxidant product and its protective effects against cardiovascular diseases have been documented. Our current study was designed to explore the cardioprotective effect of Nerol on hypoxia/reoxygenation (H/R)-induced production of reactive oxygen species (ROS) and cell apoptosis in H9c2 cells. The potential molecular mechanisms were further investigated. Methods: The cells were treated with 2.5 or 5 µM Nerol before or after H/R. Lactate dehydrogenase (LDH) release, cell viability, oxidative stress markers, and apoptotic proteins were assessed by cell counting kit-8, LDH release assay, commercial kits, and Western blot, respectively. To explore the underlying mechanism, the phosphorylation of p85 and p38, regulatory subunits of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK), was evaluated by Western blot. To further confirm that the PI3K/AKT signaling pathway participated in the cardiomyocyte protection, H9c2 cells were treated with 5 µM Nerol in the presence or absence of 5 µM BEZ235 or LY294002 followed by H/R treatment. Results: H/R remarkably induced apoptosis, LDH release and ROS production. The cell viability was suppressed via inhibiting the PI3K/AKT signaling pathway activation. By contrast, pretreatment with Nerol can neutralize these effects by activating the PI3K/AKT signaling pathway. With the addition of BEZ235 or LY294002, the inhibitory effects of Nerol were abolished. Conclusion: Nerol provided promising cardioprotective effect against H/R-induced injuries in H9c2 cells by activating the PI3K/AKT pathway.

scholarly journals Cinnamic hydroxamic acid inhibits the proliferation of gastric cancer cells via upregulation of miR 145 expression and down-regulation of P13K/Akt signaling pathway

2020 ◽  
Vol 19 (5) ◽  
pp. 957-963
Author(s):  
ShanPing Li ◽  
SenMao Hu
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Hydroxamic Acid ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Down Regulation ◽  
Protein Expressions ◽  
Dose Dependent ◽  
Cinnamic Hydroxamic Acid

Purpose: To investigate the anti-proliferative effect of cinnamic hydroxamic acid (CHA) on gastric cancer (GC) cells, and its mechanism of action.Methods: Two GC cell lines (SGC-7901 and MKN1) and normal human gastric epithelial cells (GES1) were used for this study. The GC cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM)supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. GES1 cells were cultured in RPMI medium supplemented with 10 % FBS only. Cell viability and apoptosis were determined using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The level of expression of microRNA-145 (miR-145) was determined using real-time quantitative polymerase chain reaction (qRT-PCR). Protein expressions of c-Myc, p-AKT, PI3K, p21, and matrix metalloproteinase (MMP)-2 and MMP-9were determined using Western blotting.Results: Treatment of GC cells with CHA for 72 h led to significant and dose-dependent reduction in their viability, and significant and dose-dependent increase in the number of apoptotic cells (p < 0.05). It also significantly arrested GC cell cycle at G1 phase (p < 0.05). The treatment significantly and dosedependently decreased SGC-7901 and MKN1 cell migration and invasion, and upregulated miR-145 mRNA expression (p < 0.05). The expression of miR-145 mRNA was significantly higher in MKN1 cells than in SGC-7901cells (p < 0.05). Treatment of SGC-7901 and MKN1 cells with CHA significantly downregulated protein expressions of c-Myc, MMP-2/9, PI3K and p-AKT, but upregulated p21 protein expression (p< 0.05).Conclusion: These results show that CHA inhibits the proliferation of GC cells via upregulation of miR-145 expression and down-regulation of  P13K/Akt signaling pathway. Therefore, CHA has a good potential as a therapeutic agent for the management of gastric cancer Keywords: Apoptosis, Cinnamic hydroxamic acid, Gastric cancer, Metastasis, Proliferation

Down-regulation of NDRG2 plays an important role in ATLL leukemogenesis via the PTEN-mediated PI3K/AKT signaling pathway

2015 ◽  
Vol 43 (9) ◽  
pp. S83
Author(s):  
Shingo Nakahata ◽  
Tomonaga Ichikawa ◽  
Saito Yusuke ◽  
Yasuhito Arai ◽  
Tomohiko Taki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Down Regulation
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