scholarly journals The inhibition of Bax activation-induced apoptosis by RasGRP2 via R-Ras-PI3K-Akt signaling pathway in the endothelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun-ichi Takino ◽  
Takuma Sato ◽  
Kentaro Nagamine ◽  
Takamitsu Hori
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
Ros Production ◽  
Nucleotide Exchange ◽  
Akt Signaling Pathway ◽  
Phosphoinositide 3 Kinase ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Abstract Apoptosis of endothelial cells is a very important event in various diseases and angiogenesis. We recently reported that ras guanyl nucleotide releasing protein 2 (RasGRP2), which is a guanine nucleotide exchange factor, was expressed in the human umbilical vein endothelial cells (HUVECs) and that Rap1 activation by its overexpression inhibited apoptosis by suppressing tumor necrosis factor-α induced-reactive oxygen species (ROS) production. However, other signaling pathways and roles of RasGRP2 not mediated via Rap1 are not well understood. Therefore, we compared the Mock (M) and the RasGRP2-stable overexpression (R) immortalized HUVECs using BAM7 and anisomycin, which are apoptosis inducers. BAM7 and anisomycin induced apoptosis without causing ROS production, and such apoptosis was significantly increased in M cells, but not in R cells. RasGRP2 suppressed BAM7- and anisomycin-induced apoptosis, but not via the Rap1 pathway as observed using Rap1 knockdown. Furthermore, RasGRP2 activated not only Rap1 but also R-Ras, and suppressed apoptosis by activating R-Ras-phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. The phosphorylation of Akt by RasGRP2 inhibited Bax translocation by promoting translocation of hexokinase-2 (HK-2) from cytoplasm to mitochondria. Taken together, it was suggested that RasGRP2 suppresses the Bax activation-induced apoptosis by promoting HK-2 translocation to mitochondria via R-Ras-PI3K-Akt signaling pathway.

scholarly journals The Effect and Mechanism of Emodin on the NO Secretion of Human Umbilical Vein Endothelial Cells (HUVECs) Induced by High Glucose

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Yajia Li ◽  
Qiangxiang Li ◽  
Chunyan Xie ◽  
Yanfei Huang ◽  
Limin Jia
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Signaling Pathway ◽  
High Glucose ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
High Dose ◽  
Akt Signaling Pathway ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Objective. To investigate the effects of emodin on nitric oxide (NO) secretion induced by high glucose in human umbilical vein endothelial cells (HUVECs) through the p-Akt signaling pathway. Methods. Sensitivity of cells to emodin was determined by MTT assay to establish the experimental concentrations; then, HUVECs were treated with high-dose (33.3 mmol/L) glucose (HG), HG + emodin (HG + E), HG + the Akt phosphorylation inhibitor LY294002 (HG + LY), or HG + E + LY. The p-Akt (Ser 473) expression in 48 h was analyzed using Western blot. NO effect on the secretion of HUVECs was analyzed using nitrate reductase assay. Results. The sensitive emodin concentration for HUVECs growth was 10 mol/L (P<0.05). Compared with the HG group, NO secretion was significantly higher in the HG + E group (P<0.05), whereas it was lowest in the HG + LY group (P<0.05). Compared with the HG + LY group, NO secretion was increased in the HG + E + LY group (P<0.05). The p-Akt protein expression was decreased in the HG + LY group when compared to the HG group (P<0.05), while it significantly increased in the HG + E group (P<0.05). Compared with HG + LY group, p-Akt protein expression was significantly higher in the HG + E + LY group (P<0.05). Conclusion. Emodin could improve the NO secretion of HUVECs by high glucose through the p-Akt signaling pathway.

scholarly journals Paeoniflorin Suppresses TBHP-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells via the Nrf2/HO-1 Signaling Pathway and Improves Skin Flap Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingtao Jiang ◽  
Chengji Dong ◽  
Liang Zhai ◽  
Junsheng Lou ◽  
Jie Jin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Skin Flap ◽  
Random Pattern ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Flap Survival ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Random-pattern skin flap is a vital technique frequently applied in reconstruction surgeries for its convenience and effectiveness in solving skin defects. However, ischemic necrosis, especially in the distal areas of the flap, still needs extra attention after surgery. Earlier evidence has suggested that paeoniflorin (PF) could stimulate angiogenesis and suppress ischemic cardiovascular disease. However, few studies have focused on the role of PF in flap survival. In this study, we have demonstrated that the human umbilical vein endothelial cells (HUVECs) treated with PF can alleviate tert-butyl hydroperoxide (TBHP)-stimulated cellular dysfunction and apoptosis. To better evaluate, HUVECs’ physiology, cell tube formation, migration, and adhesion were assessed. Mechanistically, PF protects HUVECs against apoptosis via stimulating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. PF also downregulates mitochondrial ROS production to reduce excessive intracellular ROS production induced by TBHP and restore TBHP-induced mitochondrial depolarization. As a result, silencing Nrf2 partially abolishes the protective effect of PF exposure on HUVECs. In in vivo experiments, the oral administration of PF was shown to have enhanced the vascularization of regenerated tissues and promote flap survival. However, the PF-mediated protection was partially lost after co-treatment with ML385, a selective Nrf2 inhibitor, suggesting that PF is a crucial modulator regulating the Nrf2/HO-1 signaling pathway. In summary, our data have provided a new insight into PF as a potential therapy for enhancing random-pattern flap viability.

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