scholarly journals α-Mangostin protects against high-glucose induced apoptosis of human umbilical vein endothelial cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Yanli Luo ◽  
Minxiang Lei
Keyword(s):  
High Glucose ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Complications ◽  
Vascular Endothelial ◽  
Apoptosis Rate ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Diabetic vascular complications result from high-glucose induced vascular endothelial cell dysfunction. There is an emerging need for novel drugs with vascular endothelial cell protective effects for the treatment of diabetic vascular complications. The present study aimed to investigate the protective effect of α-mangostin against high-glucose induced apoptosis of cultured human umbilical vein endothelial cells (HUVECs). HUVECs were treated with glucose to induce apoptosis. The expression of the apoptosis-related proteins, Bcl-2, Bax, and cleaved caspase-3, were detected by Western blotting. Ceramide concentration and acid sphingomyelinase (ASM) activity were assayed by HPLC. The cell apoptosis rate was detected by flow cytometry after staining with annexin V/propidium iodide (PI). Compared with HUVECs cultured in 5 mM glucose, cells cultured in 30 mM glucose exhibited a higher apoptosis rate, up-regulation of cleaved caspase-3 and Bax (proapoptotic proteins), down-regulation of Bcl-2 (anti-apoptotic protein), increased ceramide concentration, and enhanced ASM activity (all P<0.05). α-Mangostin (15 µM) significantly attenuated the high-glucose induced increase in apoptosis rate (8.64 ± 2.16 compared with 19.6 ± 3.54%), up-regulation of cleaved caspase-3 and Bax, down-regulation of Bcl-2, elevation of ceramide level, and enhancement of ASM activity (all P<0.05). The effects of desipramine were similar to those of α-mangostin. The protective effect of α-mangostin on high-glucose induced apoptotic damage may be mediated by an inhibition of ASM and thus a decreased level of ceramide.

scholarly journals Upregulation of Periostin Prevents High Glucose-Induced Mitochondrial Apoptosis in Human Umbilical Vein Endothelial Cells via Activation of Nrf2/HO-1 Signaling

2016 ◽  
Vol 39 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Zhi-ying Zhong ◽  
Yu Tang
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Ros Generation ◽  
Mitochondrial Apoptosis ◽  
Human Umbilical Vein ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Background/Aims: High glucose-induced oxidative damage to endothelial cells plays a central role in the pathogenesis of diabetic vascular complications. This study was undertaken to explore the role of periostin in high glucose-induced endothelial cell apoptosis and associated molecular mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (33.3 mmol/L) and examined for the expression of periostin. The effects of periostin upregulation on high glucose-induced apoptosis, mitochondrial dysfunction, and reactive oxygen species (ROS) production were determined. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) by periostin was checked. HO-1 knockdown experiments were done to confirm its role in the action of periostin in high glucose-exposed HUVECs. Results: High glucose significantly upregulated the expression of periostin in HUVECs. Enforced expression of periostin attenuated high glucose-induced apoptosis in HUVECs, as determined by TUNEL staining and caspase-3 activity assay. Periostin overexpression prevented loss of Δψm, release of mitochondrial cytochrome c, and dysregulation of Bcl-2 and Bax in high glucose-exposed HUVECs. Periostin upregulation suppressed high glucose-induced ROS generation and activated the Nrf2/HO-1 signaling. HO-1 silencing restored high glucose-induced ROS generation and apoptotic response in periostin-overexpressing HUVECs. Conclusion: Periostin mitigates high glucose-induced mitochondrial apoptosis in endothelial cells, via activation of Nrf2/HO-1 signaling and reduction of ROS formation. Further studies are warranted to explore the therapeutic potential of periostin in diabetic vascular complications.

Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis

2008 ◽  
Vol 295 (6) ◽  
pp. H2512-H2521 ◽  
Author(s):  
Satoshi Asada ◽  
Tomosaburo Takahashi ◽  
Koji Isodono ◽  
Atsuo Adachi ◽  
Hiroko Imoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Serum Withdrawal ◽  
Tyrosine Kinase 2 ◽  
Nitric Oxide Synthase 3 ◽  
Induced Apoptosis ◽  
Dicer Expression ◽  
Umbilical Vein Endothelial Cells

Although the modulated expression of Dicer is documented upon neoplastic transformation, little is known of the regulation of Dicer expression by environmental stimuli and its roles in the regulation of cellular functions in primary cells. In this study, we found that Dicer expression was downregulated upon serum withdrawal in human umbilical vein endothelial cells (HUVECs). Serum withdrawal induced a time-dependent repression of Dicer expression, which was specifically rescued by vascular endothelial cell growth factor or sphingosine-1-phosphate. When Dicer expression was silenced by short-hairpin RNA against Dicer, the cells were more prone to apoptosis under serum withdrawal, whereas the rate of apoptosis was comparable with control cells in the serum-containing condition. Real-time PCR-based gene expression profiling identified several genes, the expression of which was modulated by Dicer silencing, including adhesion and matrix-related molecules, caspase-3, and nitric oxide synthase 3 (NOS3). Dicer silencing markedly impaired migratory functions without affecting cell adhesion and repressed phosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 in adherent HUVECs. Dicer knockdown upregulated caspase-3 and downregulated NOS3 expression, and serum withdrawal indeed increased caspase-3 and decreased NOS3 expression. Furthermore, the overexpression of Dicer in HUVECs resulted in a marked reduction in apoptosis upon serum withdrawal and a decreased caspase-3 and increased NOS3 expression. The inhibition of NOS activity by Nω-nitro-l-arginine methyl ester abrogated the effect of Dicer overexpression to rescue the cells from serum withdrawal-induced apoptosis. These results indicated that serum withdrawal decreases Dicer expression, leading to an increased susceptibility to apoptosis through the regulation of caspase-3 and NOS3 expression.

The Protective Effect of Tetrahydroxystilbene Glucoside on High Glucose-Induced Injury in Human Umbilical Vein Endothelial Cells through the PI3K/Akt/eNOS Pathway and Regulation of Bcl-2/Bax

2021 ◽  
pp. 1-10
Author(s):  
Jiankun Cui ◽  
Bo Zhang ◽  
Min Gao ◽  
Baohai Liu ◽  
Cong Dai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Endothelial dysfunction plays a central role in the patho­genesis of diabetic vascular complications. 2,3,5,4′-tetra­hydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from the roots of Polygonum multiflorum Thunb, has been shown to have strong antioxidant and antiapoptotic activities. In the present study, we investigated the protective effect of TSG on apoptosis induced by high glucose in human umbilical vein endothelial cells (HUVECs) and the possible mechanisms. Our data demonstrated that TSG significantly reversed the high glucose-induced decrease in cell viability, suppressed high glucose-induced generation of intracellular reactive oxygen species (ROS), the activity of caspase-3, and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, we found that TSG not only increased the expression of Bcl-2, while decreasing Bax expression, but also activated phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) with subsequent nitric oxide production and ultimately reduced high glucose-induced apoptosis. However, the antiapoptotic effects of TSG were abrogated by pretreatment of the cells with PI3K inhibitor (LY294002) or eNOS inhibitor N<sup>G</sup>-L-nitro-arginine methyl ester, respectively. These results suggest that TSG inhibits high glucose-induced apoptosis in HUVECs through inhibition of ROS production, activation of the PI3K/Akt/eNOS pathway, and upregulation of the Bcl-2/Bax ratio, and thus may demonstrate significant potential for preventing diabetic cardiovascular complications.

scholarly journals The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells

2008 ◽  
Vol 101 (8) ◽  
pp. 1165-1170 ◽  
Author(s):  
Chia-Lun Chao ◽  
Yu-Chi Hou ◽  
Pei-Dawn Lee Chao ◽  
Ching-Sung Weng ◽  
Feng-Ming Ho
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
High Glucose ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Micromolar Concentration ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Diabetes mellitus is an important risk factor for CVD. A previous study showed that high glucose induced the apoptosis of human umbilical vein endothelial cells (HUVEC) via the sequential activation of reactive oxygen species, Jun N-terminal kinase (JNK) and caspase-3. The apoptosis cascade could be blocked by ascorbic acid at the micromolar concentration (100 μm). In addition to ascorbic acid, quercetin, the most abundant dietary flavonol, has been recently actively studied in vascular protection effects due to its antioxidant effect at low micromolar concentrations (10–50 μm). Quercetin sulfate/glucuronide, the metabolite of quercetin in blood, however, has been rarely evaluated. In the present study, we investigated the effect of quercetin sulfate/glucuronide on the prevention of high glucose-induced apoptosis of HUVEC. HUVEC were treated with media containing high glucose (33 mm) in the presence or absence of ascorbic acid (100 μm) or quercetin sulfate/glucuronide (100 nm, 300 nm and 1 μm). For the detection of apoptosis, a cell death detection ELISA assay was used. The level of intracellular H2O2 was measured by flow cytometry. JNK and caspase-3 were evaluated by a kinase activity assay and Western blot analysis. The results showed that high glucose-induced apoptosis was inhibited by quercetin sulfate/glucuronide in a dose-dependent manner. The effect of quercetin sulfate/glucuronide on H2O2 quenching, inhibition of JNK and caspase-3 activity at the nanomolar concentration (300 nm) was similar to that of ascorbic acid at the micromolar concentration (100 μm). The findings of the present study may shed light on the pharmacological application of quercetin in CVD.

scholarly journals Isosamidin from Peucedanum japonicum Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 531
Author(s):  
Moon Ho Do ◽  
Jae Hyuk Lee ◽  
Jongmin Ahn ◽  
Min Jee Hong ◽  
Jinwoong Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Complications ◽  
In Vivo Models ◽  
Human Umbilical Vein ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Methylglyoxal (MGO) is a highly reactive metabolite of glucose. Elevated levels of MGO induce the generation of reactive oxygen species (ROS) and cause cell death in endothelial cells. Vascular endothelial cell damage by ROS has been implicated in the progression of diabetic vascular complications, cardiovascular diseases, and atherosclerosis. In this study, the protective effect of isosamidin, isolated from Peucedanum japonicum roots, on MGO-induced apoptosis was investigated using human umbilical vein endothelial cells (HUVECs). Among the 20 compounds isolated from P. japonicum, isosamidin showed the highest effectiveness in inhibiting MGO-induced apoptosis of HUVECs. Pretreatment of HUVECs with isosamidin significantly prevented the generation of ROS and cell death induced by MGO. Isosamidin prevented MGO-induced apoptosis in HUVECs by downregulating the expression of Bax and upregulating the expression of Bcl-2. MGO treatment activated mitogen-activated protein kinases (MAPKs), such as p38, c-Jun N terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). In contrast, pretreatment with isosamidin strongly inhibited the activation of p38 and JNK. Furthermore, isosamidin caused the breakdown of the crosslinks of the MGO-derived advanced glycation end products (AGEs). These findings suggest that isosamidin from P. japonicum may be used as a preventive agent against MGO-mediated endothelial dysfunction in diabetes. However, further study of the therapeutic potential of isosamidin on endothelial dysfunction needs to explored in vivo models.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 473-482 ◽  
Author(s):  
Si Sun ◽  
Le Liu ◽  
Xiaojun Tian ◽  
Yanghongyun Guo ◽  
Yingkang Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Vascular Complications ◽  
Flavonoid Glycoside ◽  
Inflammatory Factors ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractEndothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

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