Klotho protein inhibits H2O2-induced oxidative injury in endothelial cells via regulation of PI3K/AKT/Nrf2/HO-1 pathways

2019 ◽  
Vol 97 (5) ◽  
pp. 370-376 ◽  
Author(s):  
Wei Cui ◽  
Bin Leng ◽  
GaoPin Wang
Keyword(s):  
Endothelial Cells ◽  
Oxidative Damage ◽  
Nuclear Translocation ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Heme Oxygenase 1 ◽  
Protective Mechanism ◽  
Vascular Endothelial ◽  
Necrosis Factor Alpha ◽  
Klotho Protein

Klotho protein secreted in the blood could act as a hormone to regulate various target organs and have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells. The purpose of this study was to investigate the protective mechanism of Klotho protein on oxidative damage of vascular endothelial cells induced by H2O2. Klotho protein significantly enhanced human umbilical vein endothelial cells viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 (HO-1)), scavenged reactive oxygen species, and inhibited tumor necrosis factor alpha and interleukin 6 secretion. Klotho protein also reduced the rate of apoptosis of cells and improved the function of vascular endothelial cells (increased nitric oxide secretion). Klotho protein activated nuclear translocation of Nrf2 and increased HO-1 expression. Klotho protein also activated phosphorylation of protein kinase B (AKT), whereas the addition of LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked Klotho-protein-induced Nrf2/HO-1 activation and cytoprotection. Klotho protein enhanced the antioxidant defense ability of the cells by activating the PI3K/AKT pathway, which upregulated the expression of Nrf2/HO-1, thereby inhibiting H2O2-induced oxidative damage.

scholarly journals The Activation of Nrf2 and Its Downstream Regulated Genes Mediates the Antioxidative Activities of Xueshuan Xinmaining Tablet in Human Umbilical Vein Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Lingxin Xiong ◽  
Jingshu Xie ◽  
Chenxue Song ◽  
Jinping Liu ◽  
Jingtong Zheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Critical Role ◽  
Vascular Endothelial Cell ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Vascular Endothelial ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Epidemiological studies have verified the critical role that antioxidative stress plays in protecting vascular endothelial cells. The aims of the present study were to investigate the antioxidative activities and differential regulation of nuclear erythroid-related factor 2- (Nrf2-) mediated gene expression by Xueshuan Xinmaining Tablet (XXT), a traditional Chinese medicine with the effect of treating cardiovascular diseases. The antioxidative activities of XXT were investigated using quantitative real-time PCR (qPCR), a PCR array, and western blotting. Our results indicated that XXT exhibited potent antioxidative activities by suppressing the levels of hydrogen peroxide- (H2O2-) induced reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs). We were also conscious of strong Nrf2-mediated antioxidant induction. XXT enhanced the expressions of Keap1, Nrf2, and Nrf2-mediated genes, such as glutamate-cysteine ligase modifier subunit (GCLM), NAD(P)H: quinine oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutathione peroxidase (GPX) in HUVECs. In summary, XXT strongly activated Nrf2 and its downstream regulated genes, which may contribute to the antioxidative and vascular endothelial cell protective activities of XXT.

scholarly journals Protective Effect of Flavonoids from a Deep-Sea-Derived Arthrinium sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 712
Author(s):  
Jia-Rong Hou ◽  
Yan-Hong Wang ◽  
Ying-Nan Zhong ◽  
Tong-Tong Che ◽  
Yang Hu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Deep Sea ◽  
Nuclear Translocation ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Oxidative Injury ◽  
Vascular Endothelial ◽  
Level Increase ◽  
Induced Apoptosis

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment.

scholarly journals Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Purum Kang ◽  
Seung Ho Han ◽  
Hea Kyung Moon ◽  
Jeong-Min Lee ◽  
Hyo-Keun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Channel Blocker ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Carbonyl Cyanide ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

Abstract 5456: Vascular Endothelial Cells Endothelin-1 Deficiency Decreased Vascular Protection in Atherosclerosis Mouse Model

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dyah Wulan Anggrahini ◽  
Noriaki Emoto ◽  
Kazuhiko Nakayama ◽  
Bambang Widyantoro ◽  
Kazuya Miyagawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vessel Wall ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Vascular Wall ◽  
Protective Mechanism ◽  
Vascular Endothelial ◽  
Vascular Protection ◽  
Plaque Instability

Endothelium plays important role in protective mechanism of vascular wall. The balance between endothelin-1 (ET-1) and nitric oxide provide endothelial barrier to lipoprotein retain and macrophage recruitment. In contrasts, ET-1 is also a strong vasoconstrictor. In this study, we aim to determine the role of vascular endothelial cells-derived ET-1 in the development of atherosclerosis. For that purpose, we crossbred Vascular Endothelial Cells-specific ET-1 Knockout (VEETKO) mice to ApoEKO mice. ApoE/VEET-DKO exhibited significantly lower ET-1 plasma and mRNA level as compared to ApoEKO mice. No significant differences of blood pressure, plasma cholesterol or lipid profiles were observed in both mice. Surprisingly, after 8 weeks of western diet, we found that the atherosclerotic lesion was exaggerated in the aortic sinus and brachiochepalic artery of ApoE/VEET-DKO mice (n=7) as compared to those of ApoEKO mice (n=7) (ratio/vessel wall, 0.93±0.13vs.0.49±0.09, p<0.05). We further showed the increase in macrophage plaque content and peritoneal macrophage recruitment in DKO mice. To understand the mechanism of vascular protection, we found lower eNOS mRNA level in DKO mice despite only lower tendency of ETB receptor expression. Functionally, the mice lacking ET-1 in endothelial cells showed impaired NO-mediated endothelial function. Decreased vascular protection further led to increase plaque instability in DKO mice. Here we showed that plaque of DKO mice was more lipid enrich as compared to that of ApoEKO (ratio/lesion, 0.56±0.03vs.0.42±0.04, p<0.05). Moreover, lack of ET-1 significantly reduced matrix synthesis following lower SMCs accumulation in the lesion (ratio/vessel wall, 0.28±0.06vs.0.57±0.08, p<0.05), which was mediated by TGFβ. Interestingly, despite similar advance-typed lesion formed, 15% of DKO mice exhibited plaque hemorrhage in brachiochepalic artery. In conclusion, we demonstrated the increase in atherosclerosis and plaque instability in our model. This further suggests that ET-1 produced from vascular endothelial cells is required for protective mechanism in vascular wall in balance with nitric oxide production. Our data imply for the careful monitoring in the use of ET receptor antagonist in clinical setting.

scholarly journals Oxidized polyamines and the growth of human vascular endothelial cells. Prevention of cytotoxic effects by selective acetylation

1987 ◽  
Vol 242 (2) ◽  
pp. 347-352 ◽  
Author(s):  
D M L Morgan
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Amine Oxidase ◽  
Umbilical Vein ◽  
Polyamine Oxidase ◽  
Oxidation Products ◽  
Vascular Endothelial ◽  
Cytotoxic Effects ◽  
Naturally Occurring ◽  
Aminopropyl Group

The responses of human umbilical-vein vascular endothelial cells in culture to the naturally occurring polyamines spermine, spermidine and putrescine, their acetyl derivatives and oxidation products were examined. In the absence of human polyamine oxidase, exposure of cells to polyamines (up to 160 microM) had no adverse effects. In the presence of polyamine oxidase, spermine and spermidine were cytotoxic, but putrescine was not. Acetylation of the aminopropyl group of spermidine or both aminopropyl groups of spermine prevented this cytotoxicity. The amino acids corresponding to the polyamines, representing a further stage of oxidation, were also without effect. The cytotoxic effects were irreversible. Use of bovine serum amine oxidase in place of the human enzyme gave qualitatively similar results.

Thrombin receptor 14-amino acid peptide binds to endothelial cells and stimulates calcium transients

1992 ◽  
Vol 263 (5) ◽  
pp. L595-L601 ◽  
Author(s):  
C. Tiruppathi ◽  
H. Lum ◽  
T. T. Andersen ◽  
J. W. Fenton ◽  
A. B. Malik
Keyword(s):  
Endothelial Cells ◽  
Intracellular Calcium ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Calcium Transients ◽  
Cell Protein ◽  
Affinity Constant ◽  
Thrombin Receptor ◽  
Vascular Endothelial ◽  
Amino Terminal

We examined the binding characteristics of the recently described thrombin receptor amino-terminal peptide, SFLLRNPNDKYEPF (T. K. H. Vu, D. T. Hung, V. I. Wheaton, and S. R. Coughlin. Cell 64: 1057-1068, 1991), termed TRP-14, and its effect in activating intracellular calcium transients in pulmonary vascular endothelial cells. Binding of 125I-labeled TRP-14 was found to be saturable with a affinity constant of 2 microM and maximum binding of 41 pmol/mg of cell protein. The 125I-labeled TRP-14 also interacted with bovine pulmonary microvessel endothelial cells, human umbilical vein endothelial cells, and porcine pulmonary artery smooth muscle cells. Binding of 125I-labeled diisopropylphosphoryl (DIP)-alpha-thrombin, which is catalytically inactive but binds to thrombin receptors, was not inhibited by TRP-14 or vice versa, indicating that TRP-14 did not compete for the alpha-thrombin binding site(s) on the endothelial cell surface. TRP-14 (> 1 microM) increased the concentration of intracellular calcium ([Ca2+]i) in endothelial cells with kinetics similar to the increase in [Ca2+]i triggered by alpha-thrombin. In contrast, DIP-alpha-thrombin did not increase [Ca2+]i and also did not prevent the rise in [Ca2+]i induced by the subsequent challenge with either TRP-14 or alpha-thrombin. Because the generation of TRP-14 by the proteolytically active forms of thrombin stimulated a rise in endothelial [Ca2+]i, TRP-14 may be the agonist responsible for the activation of the alpha-thrombin receptor in pulmonary vascular endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals S-adenosyl methionine prevents endothelial dysfunction by inducing heme oxygenase-1 in vascular endothelial cells

2013 ◽  
Vol 36 (4) ◽  
pp. 376-384 ◽  
Author(s):  
Sun Young Kim ◽  
Seok Woo Hong ◽  
Mi-Ok Kim ◽  
Hyun-Sik Kim ◽  
Jung Eun Jang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
Vascular Endothelial Cells ◽  
Heme Oxygenase 1 ◽  
Vascular Endothelial ◽  
Adenosyl Methionine
Sign in / Sign up

Export Citation Format

Share Document