scholarly journals Ang (1–7) Protects Islet Endothelial Cells from Palmitate-Induced Apoptosis by AKT, eNOS, p38 MAPK, and JNK Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Li Yuan ◽  
Chun-Li Lu ◽  
Ying Wang ◽  
Yang Li ◽  
Xiao-Ya Li
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
P38 Mapk ◽  
Reactive Oxygen ◽  
Treated Group ◽  
Ros Production ◽  
Oxygen Species ◽  
Concomitant Reduction ◽  
Jnk Inhibitors ◽  
Induced Apoptosis

This study aimed to explore the effect of angiotensin (1–7) (Ang (1–7)) on palmitate-induced apoptosis in islet endothelial cells and the mechanism of action. MS-1 cells were treated with palmitate in the presence or absence of Ang (1–7). The percentage of apoptotic cells was determined by DNA fragmentation and flow cytometry. Reactive oxygen species (ROS) production was measured using a Reactive Oxygen Species Assay Kit. Expression of AKT, eNOS, C-Jun N-terminal kinase (JNK), and p38 was detected by western blotting. Compared with palmitate treated group, palmitate-induced apoptosis was decreased in MS-1 cells which were preincubated with Ang (1–7) (P<0.05). Palmitate decreased the phosphorylation of AKT and eNOS, and Ang (1–7) increased the phosphorylation of these kinases (P<0.05), with a concomitant reduction in MS-1 cells apoptosis. Ang (1–7) also inhibited the palmitate-induced ROS production and attenuated the apoptosis-related signaling molecule JNK and p38 activation (allP<0.05). PI3K/AKT, eNOS, p38 MAPK, and JNK inhibitors blocked the antilipoapoptosis of Ang (1–7) (allP<0.05). Our findings suggest that Ang (1–7) reduces palmitate-induced islet endothelial cells apoptosis. AKT/eNOS/NO signaling and JNK and p38 pathway are involved in the Ang (1–7)-mediated modulation of islet endothelial cells lipoapoptosis.

scholarly journals Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species

2021 ◽  
Vol 22 (11) ◽  
pp. 6044
Author(s):  
Xiaoling Li ◽  
Gregor Römer ◽  
Raphaela P. Kerindongo ◽  
Jeroen Hermanides ◽  
Martin Albrecht ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen ◽  
Cyclic Stretch ◽  
Cell Permeability ◽  
Ros Production ◽  
Oxygen Species ◽  
Barrier Dysfunction ◽  
Human Coronary Artery ◽  
Oxidative Effect

SGLT-2i’s exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i’s empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) exert an anti-oxidative effect and alleviate cyclic stretch-induced endothelial permeability in human coronary artery endothelial cells (HCAECs). HCAECs were pre-incubated with one of the SGLT-2i’s (1 µM EMPA, 1 µM DAPA and 3 µM CANA) for 2 h, followed by 10% stretch for 24 h. HCAECs exposed to 5% stretch were considered as control. Involvement of ROS was measured using N-acetyl-l-cysteine (NAC). The sodium-hydrogen exchanger 1 (NHE1) and NADPH oxidases (NOXs) were inhibited by cariporide, or GKT136901, respectively. Cell permeability and ROS were investigated by fluorescence intensity imaging. Cell permeability and ROS production were increased by 10% stretch; EMPA, DAPA and CANA decreased this effect significantly. Cariporide and GKT136901 inhibited stretch-induced ROS production but neither of them further reduced ROS production when combined with EMPA. SGLT-2i’s improve the barrier dysfunction of HCAECs under enhanced stretch and this effect might be mediated through scavenging of ROS. Anti-oxidative effect of SGLT-2i’s might be partially mediated by inhibition of NHE1 and NOXs.

scholarly journals Imbalanced Production of Reactive Oxygen Species and Mitochondrial Antioxidant SOD2 in Fabry Disease-Specific Human Induced Pluripotent Stem Cell-Differentiated Vascular Endothelial Cells

2017 ◽  
Vol 26 (3) ◽  
pp. 513-527 ◽  
Author(s):  
Wei-Lien Tseng ◽  
Shih-Jie Chou ◽  
Huai-Chih Chiang ◽  
Mong-Lien Wang ◽  
Chian-Shiu Chien ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Fabry Disease ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Oxygen Species ◽  
Ampk Activity ◽  
Induced Pluripotent

Fabry disease (FD) is an X-linked inherited lysosomal storage disease caused by α-galactosidase A (GLA) deficiency. Progressive intracellular accumulation of globotriaosylceramide (Gb3) is considered to be pathogenically responsible for the phenotype variability of FD that causes cardiovascular dysfunction; however, molecular mechanisms underlying the impairment of FD-associated cardiovascular tissues remain unclear. In this study, we reprogrammed human induced pluripotent stem cells (hiPSCs) from peripheral blood cells of patients with FD (FD-iPSCs); subsequently differentiated them into vascular endothelial-like cells (FD-ECs) expressing CD31, VE-cadherin, and vWF; and investigated their ability to form vascular tube-like structures. FD-ECs recapitulated the FD pathophysiological phenotype exhibiting intracellular Gb3 accumulation under a transmission electron microscope. Moreover, compared with healthy control iPSC-derived endothelial cells (NC-ECs), reactive oxygen species (ROS) production considerably increased in FD-ECs. Microarray analysis was performed to explore the possible mechanism underlying Gb3 accumulation-induced ROS production in FD-ECs. Our results revealed that superoxide dismutase 2 (SOD2), a mitochondrial antioxidant, was significantly downregulated in FD-ECs. Compared with NC-ECs, AMPK activity was significantly enhanced in FD-ECs. Furthermore, to investigate the role of Gb3 in these effects, human umbilical vein endothelial cells (HUVECs) were treated with Gb3. After Gb3 treatment, we observed that SOD2 expression was suppressed and AMPK activity was enhanced in a dose-dependent manner. Collectively, our results indicate that excess accumulation of Gb3 suppressed SOD2 expression, increased ROS production, enhanced AMPK activation, and finally caused vascular endothelial dysfunction. Our findings suggest that dysregulated mitochondrial ROS may be a potential target for treating FD.

scholarly journals Inhibition of p38 MAPK sensitizes tumour cells to cisplatin‐induced apoptosis mediated by reactive oxygen species and JNK

2013 ◽  
Vol 5 (11) ◽  
pp. 1759-1774 ◽  
Author(s):  
Lorena Pereira ◽  
Ana Igea ◽  
Begoña Canovas ◽  
Ignacio Dolado ◽  
Angel R. Nebreda
Keyword(s):  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Reactive Oxygen ◽  
Tumour Cells ◽  
Oxygen Species ◽  
Induced Apoptosis

scholarly journals Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Sun ◽  
Tongsheng Chen ◽  
Xiaoping Wang ◽  
Yun Chen ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Temporal Dynamics ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

scholarly journals Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry

2012 ◽  
Vol 87 (3) ◽  
pp. 1733-1749 ◽  
Author(s):  
Virginie Bottero ◽  
Sayan Chakraborty ◽  
Bala Chandran
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Kaposi's Sarcoma ◽  
Reactive Oxygen ◽  
Kaposi’S Sarcoma ◽  
Target Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Kshv Infection ◽  
D Cells

ABSTRACTThe entry of Kaposi's sarcoma-associated herpesvirus (KSHV) into human dermal microvascular endothelial cells (HMVEC-d), naturalin vivotarget cells, via macropinocytosis is initiated through a multistep process involving the binding of KSHV envelope glycoproteins with cell surface α3β1, αVβ3, and αVβ5 integrin molecules and tyrosine kinase ephrin-A2 receptor, followed by the activation of preexisting integrin-associated signaling molecules such as focal adhesion kinase (FAK), Src, c-Cbl, phosphoinositide 3-kinase (PI-3K), and Rho-GTPases. Many viruses, including KSHV, utilize cellular reactive oxygen species (ROS) for viral genomic replication and survival within host cells; however, the role of ROS in early events of viral entry and the induction of signaling has not been elucidated. Here we show that KSHV induced ROS production very early during the infection of HMVEC-d cells and that ROS production was sustained over the observation period (24 h postinfection). ROS induction was dependent on the binding of KSHV to the target cells, since pretreatment of the virus with heparin abolished ROS induction. Pretreatment of HMVEC-d cells with the antioxidantN-acetylcysteine (NAC) significantly inhibited KSHV entry, and consequently gene expression, without affecting virus binding. In contrast, H2O2treatment increased the levels of KSHV entry and infection. In addition, NAC inhibited KSHV infection-induced translocation of αVβ3 integrin into lipid rafts, actin-dependent membrane perturbations, such as blebs, observed during macropinocytosis, and activation of the signal molecules ephrin-A2 receptor, FAK, Src, and Rac1. In contrast, H2O2treatment increased the activation of ephrin-A2, FAK, Src, and Rac1. These studies demonstrate that KSHV infection induces ROS very early during infection to amplify the signaling pathways necessary for its efficient entry into HMVEC-d cells via macropinocytosis.

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