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 Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner

Circulation ◽  
2007 ◽  
Vol 116 (14) ◽  
pp. 1585-1595 ◽  
Author(s):  
Ping Song ◽  
Yong Wu ◽  
Jian Xu ◽  
Zhonglin Xie ◽  
Yunzhou Dong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Small Interfering Rna ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
Chromosome 10 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Phosphatase And Tensin Homologue ◽  
Interfering Rna

Background— Oxidative stress plays a causal role in vascular injury in diabetes mellitus, but the mechanisms and targets remain poorly understood. Methods and Results— Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO − ) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Furthermore, protein kinase B/Akt inhibition induced by ONOO − or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO − . In addition, exposure of human umbilical vein endothelial cells to ONOO − or high glucose remarkably increased Ser428 phosphorylation of LKB1, a tumor suppressor. Interestingly, the ONOO − -enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA. Consistently, LKB1 phosphorylated PTEN at Ser380/Thr382/383 in vitro, suggesting that LKB1 might act as an upstream kinase for PTEN. Compared with nondiabetic mice, the levels of PTEN, LKB1-Ser428 phosphorylation, and 3-nitrotyrosine (a biomarker of ONOO − ) were significantly increased in the aortas of streptozotocin-induced diabetic mice, which was in parallel with a reduction in Akt-Ser473 phosphorylation and an increase in apoptosis. Furthermore, administration of PTEN-specific small interfering RNA suppressed diabetes-enhanced apoptosis and Akt inhibition. Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO − formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas. Conclusion— We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO − -mediated LKB1-dependent PTEN activation.

scholarly journals Antioxidant Blueberry Anthocyanins Induce Vasodilation via PI3K/Akt Signaling Pathway in High-Glucose-Induced Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 21 (5) ◽  
pp. 1575 ◽  
Author(s):  
Wuyang Huang ◽  
Ruth Paulina Hutabarat ◽  
Zhi Chai ◽  
Tiesong Zheng ◽  
Weimin Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Akt Signaling Pathway ◽  
Peroxisome Proliferator Activated Receptor

Blueberries are rich in antioxidant anthocyanins. The hypotensive effects of blueberry anthocyanins in endothelial cells was investigated here. Pretreatment with blueberry anthocyanin extract, malvidin, malvidin-3-glucoside, and malvidin-3-galactoside significantly ameliorated high-glucose-induced damage by enhancing endogenous antioxidant superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), lowering reactive oxygen species (ROS) generation and NADPH oxidase isoform 4 (NOX4) expression, and increasing the cell vitalities. They also effectively induced a vasodilatory effect by increasing the vasodilator nitric oxide (NO) and its promoters endothelial NO synthase (eNOS) and peroxisome proliferator-activated receptor-γ (PPARγ) levels as well as by decreasing the vasoconstrictor angiotensin-converting enzyme (ACE), xanthine oxidase-1 (XO-1), and low-density lipoprotein (LDL) levels. The activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the breakdown of protein kinase C zeta (PKCζ) pathway were involved in the bioactivities. The results indicated blueberry anthocyanins protected endothelial function against high-glucose (HG) injury via antioxidant and vasodilatory mechanisms, which could be promising molecules as a hypotensive nutraceutical for diabetes patients.

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.

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