scholarly journals Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3372 ◽  
Author(s):  
Yan-Hui Shen ◽  
Li-Ying Wang ◽  
Bao-Bao Zhang ◽  
Qi-Ming Hu ◽  
Pu Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Jnk Pathway

Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V–FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: A novel antioxidative mechanism

2007 ◽  
Vol 97 (01) ◽  
pp. 88-98 ◽  
Author(s):  
Christina Barja-Fidalgo ◽  
Vany Nascimento-Silva ◽  
Maria Arruda ◽  
Iolanda Fierro
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Ros Generation ◽  
Oxygen Species ◽  
Lipoxin A4 ◽  
Pre Treatment

SummaryLipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A4 analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1–100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47phox to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF-κB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

scholarly journals HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction Implications for Statin Treatment in HIV Patients

2019 ◽  
Vol 125 (9) ◽  
pp. 805-820 ◽  
Author(s):  
Sarvesh Chelvanambi ◽  
Samir K. Gupta ◽  
Xingjuan Chen ◽  
Bradley W. Ellis ◽  
Bernhard F. Maier ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Antiretroviral Therapy ◽  
Cardiovascular Diseases ◽  
Extracellular Vesicles ◽  
Reactive Oxygen ◽  
Statin Treatment ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Hiv Patients

Rationale: Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role in cardiovascular diseases. A possible cofactor may be persistence of the early HIV response gene Nef, which we have demonstrated recently to persist in the lungs of HIV+ patients on antiretroviral therapy. Previously, we have reported that HIV strains with Nef, but not Nef-deleted HIV strains, cause endothelial proinflammatory activation and apoptosis. Objective: To characterize mechanisms through which HIV-Nef leads to the development of cardiovascular diseases using ex vivo tissue culture approaches as well as interventional experiments in transgenic murine models. Methods and Results: Extracellular vesicles derived from both peripheral blood mononuclear cells and plasma from HIV+ patient blood samples induced human coronary artery endothelial cells dysfunction. Plasma-derived extracellular vesicles from antiretroviral therapy+ patients who were HIV-Nef+ induced significantly greater endothelial apoptosis compared with HIV-Nef-plasma extracellular vesicles. Both HIV-Nef expressing T cells and HIV-Nef-induced extracellular vesicles increased transfer of cytosol and Nef protein to endothelial monolayers in a Rac1-dependent manner, consequently leading to endothelial adhesion protein upregulation and apoptosis. HIV-Nef induced Rac1 activation also led to dsDNA breaks in endothelial colony forming cells, thereby resulting in endothelial colony forming cell premature senescence and endothelial nitric oxide synthase downregulation. These Rac1-dependent activities were characterized by NOX2-mediated reactive oxygen species production. Statin treatment equally inhibited Rac1 inhibition in preventing or reversing all HIV-Nef-induction abnormalities assessed. This was likely because of the ability of statins to block Rac1 prenylation as geranylgeranyl transferase inhibitors were effective in inhibiting HIV-Nef-induced reactive oxygen species formation. Finally, transgenic expression of HIV-Nef in endothelial cells in a murine model impaired endothelium-mediated aortic ring dilation, which was then reversed by 3-week treatment with 5 mg/kg atorvastatin. Conclusions: These studies establish a mechanism by which HIV-Nef persistence despite antiretroviral therapy could contribute to ongoing HIV-related vascular dysfunction, which may then be ameliorated by statin treatment.

The Requirement of Reactive Oxygen Species Generation in the Apoptosis of Leukemia Cells Induced by 2-Methoxyestradiol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4370-4370
Author(s):  
Guo Kunyuan ◽  
Miaorong She ◽  
Haiyan Hu ◽  
Xinqing Niu ◽  
Sanfang Tu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Leukemia Cell ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract 2-Methoxyestradiol (2-ME) is a new anticancer agent currently under investigation for treatment of leukemia. We evaluated the effects of 2-ME-induced apoptosis in two myeloid leukemia cell lines (U937 and HL-60) in association with reactive oxygen species (ROS) generation. We found that 2-ME resulted in viability decrease in a dose-dependent manner, generated ROS: nitric oxide and superoxide anions, and mitochondria damage. 2-ME-induced apoptosis correlated with increase in ROS. Quenching of ROS with N-acetyl-L-cysteine protected leukemia cells from the cytotoxicity of 2-ME and prevented apoptosis induction by 2-ME. Furthermore, addition of manumycin, a farnesyltransferase inhibitor, demonstrated by our previous studies that induced apoptosis of leukemic cells and induced ROS, significantly enhanced the apoptosis-induced by 2-ME. In conclusion, cellular ROS generation play an important role in the cytotoxic effect of 2-ME. It is possible to use ROS-generation agents such as manumycin to enhance the antileukemic effect. Such a combination strategy need the further in vivo justify and may have potential clinical application.

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 Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 316 ◽  
Author(s):  
Wanchun Su ◽  
Lei Wang ◽  
Xiaoting Fu ◽  
Liying Ni ◽  
Delin Duan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protective Effect ◽  
Reactive Oxygen ◽  
Saccharina Japonica ◽  
Intracellular Reactive Oxygen Species ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Oxygen Species

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.

Human Herpesvirus-8 (HHV-8/KSHV) Induces Reactive Oxygen Species in Endothelial Cells That Facilitate Virus Infection.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 605-605 ◽  
Author(s):  
Jian Feng Wang ◽  
Xuefeng Zhang ◽  
Bala Chandran ◽  
Jerome E. Groopman
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Virus Entry ◽  
Reactive Oxygen ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Ros Generation ◽  
Target Cells ◽  
Oxygen Species ◽  
Herpesvirus 8

Abstract Reactive oxygen species (ROS) can activate replication of certain viruses, induce the production of various inflammatory mediators and play a critical role in carcinogenesis and tumor development. Kaposi’s sarcoma (KS) is the most prevalent HIV-associated cancer and is caused by infection with human herpesvirus-8 (HHV-8/KSHV). KS tissue has been reported to possess increased levels of ROS. We studied if ROS generation is related to HHV-8 infection and its role in virus entry into endothelial cells. Incubation of dermal microvascular endothelial cells (DMECs) with highly purified HHV-8 induced rapid increases in the production of intracellular hydrogen peroxide (H2O2), one of the major forms of ROS. Intracellular H2O2 was also induced by the treatment of DMECs with the HHV-8 envelope glycoprotein B (gB). The gB protein possesses an RGD motif, binds to the integrin molecules, alpha3 and beta1, and is a major mediator of virus entry into target cells. To test if it was integrin ligation that induces the production of ROS, we treated DMECs with fibronectin or laminin, the respective natural ligands for alpha3 and beta1 integrins. We observed a similar induction of intracellular ROS in DMECs by either matrix protein. These results indicated that the HHV-8-induced production of ROS was, at least in part, mediated by stimulation of integrins through the RGD-containing viral gB protein. ROS have recently been shown to function as second messengers in cellular signaling. To assess at which steps of cell signaling ROS may be functioning, we studied the signaling cascade in DMECs activated by the HHV-8 gB protein. Previous studies have shown that HHV-8, through gB/integrin interaction, induces cytoskeletal rearrangement and activates focal adhesion kinase (FAK), Src kinase and Akt, which are critical for virus entry into the target cells. We found that the activation of FAK, c-Src or Akt by this viral protein was inhibited by pretreatment with N-acetyl-L-cysteine (NAC), a potent thiol antioxidant. These results suggested that generation of ROS was involved in HHV-8-triggered signaling. We next examined if a change in ROS production modulated HHV-8 virus entry. We used green fluorescent protein (GFP)-labeled HHV-8 at a multiplicity of infection of 5–6, and quantitated the infection by fluorescence analysis of the DMECs. Short term exposure to low concentrations of H2O2 enhanced HHV-8 infection in DMECs, while treatment with NAC significantly decreased infection. These data indicated that ROS generation participated in HHV-8-mediated signaling and entry into target cells. Our study demonstrates a novel role of ROS in virus pathogenesis and provides a framework for the development of novel antioxidant strategies in AIDS-KS treatment.

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