Protective effects of a free radical scavenger, MCI-186, on high-glucose-induced dysfunction of human dermal microvascular endothelial cells

2004 ◽  
Vol 12 (6) ◽  
pp. 607-612 ◽  
Author(s):  
Dong Jiaojun ◽  
Yoshihiro Takami ◽  
Hideharu Tanaka ◽  
Ryo Yamaguchi ◽  
Guo Jingping ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Free Radical ◽  
High Glucose ◽  
Free Radical Scavenger ◽  
Microvascular Endothelial Cells ◽  
Radical Scavenger ◽  
Protective Effects ◽  
Microvascular Endothelial

Stimulation of Tetrahydrobiopterin Synthesis by 17β-Estradiol in Brain Microvascular Endothelial Cells

Pteridines ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 129-132
Author(s):  
Kazuhiro Shiota ◽  
Masakazu Ishii ◽  
Toshinori Yamamoto ◽  
Shunichi Shimizu ◽  
Yuji Kiuchi
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Microvascular Endothelial Cells ◽  
No Production ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
17Β Estradiol ◽  
Microvascular Endothelial

Abstract The purpose of this study was to examine whether 17β-estradiol stimulates the synthesis of tetrahydrobiopterin : BH4), which is one of the cofactors of nitric oxide (NO) synthase, in mouse brain microvascular endothelial cells. Addition of 17()-estradiol to endothelial cells time- and concentration-dependently increased intracellular BH4 level. 17β-Estradiol also stimulated the mRNA level of GTP-cyclohydrolase I (GTPCH), which is a rate-limiting enzyme of the de novo BH4 synthetic pathway. In addition, the 17β-estradiol-induced expression of GTPCH mRNA was strongly attenuated by treatment with an inhibitor of 17β-estradiol receptor 4-hydroxy-tamoxlfen. These results suggest that 17β-estradiol stimulates BH4 synthesis through the induction of GTPCH by tamoxifensensitive receptor in vascular endothelial cells. The 17β-estradiol-induced increase in BH4 level might be implicated in not only NO production, but also protective effects of 17β-estradiol against ischemic brain damage and atherosclerosis, since BH4 is an intracellular antioxidant.

Autophagy inhibits high glucose induced cardiac microvascular endothelial cells apoptosis by mTOR signal pathway

APOPTOSIS ◽  
2017 ◽  
Vol 22 (12) ◽  
pp. 1510-1523 ◽  
Author(s):  
Zheng Zhang ◽  
Shenwei Zhang ◽  
Yong Wang ◽  
Ming Yang ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Signal Pathway ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

Abstract 269: Exendin-4 Prevents Glucose-induced Secretion of Tissue Transglutaminase-2 from Cardiac Microvascular Endothelial Cells: Potential Role in the Prevention of Matrix Remodeling in Diabetes

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Ali S Shihab ◽  
Vanitra A Richardson ◽  
Betsy B Dokken
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
High Glucose ◽  
Tissue Transglutaminase ◽  
Vascular Complications ◽  
Transglutaminase 2 ◽  
Conditioned Media ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

Diabetes causes endothelial dysfunction, which is the initial trigger for vascular complications in diabetic patients. Hyperglycemia initiates a cascade of events that alters protein expression and secretion by endothelial cells. Tissue transglutaminase-2 (tTG2) is an enzyme that under physiologic conditions is sequestered inside the endothelial cell, but under pathologic conditions causing decreased bioavailability of nitric oxide, tTG2 is secreted, activated, and catalyzes irreversible crosslinking of proteins in the extracellular matrix (ECM). Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist, used in the treatment of type 2 diabetes, which has vasculo-protective effects. We hypothesized that hyperglycemic stress would induce secretion of tTG2, and that this effect would be attenuated by Ex-4. Mouse cardiac microvascular endothelial cells (MCECs) were serum-starved and exposed to control (5.5 mM glucose) or hyperglycemic (25 mM glucose) conditions, with or without Ex-4 (10 nM) x 72 hrs. Proteins from conditioned media were isolated, trypsinized, and analyzed using LC-MS/MS (LTQ Orbitrap Velos). Immunoblots from cell homogenate were probed for tTG protein expression. Conditioned media from MCECs exposed to high-glucose but not Ex-4 contained tTG2, which was absent in media from cells exposed to high-glucose and Ex-4, as well as in media from control cells, suggesting that Ex-4 prevented the secretion of tTG2 induced by hyperglycemic stress. Protein expression in cell lysate was not different. These findings may have important implications for the etiology of diabetic vascular complications, and for the role of Ex-4 to prevent the pathologic ECM remodeling associated with diabetic vasculopathy. Further studies are ongoing to determine the mechanisms of glucose-induced secretion of tTG2, as well as the mechanisms by which Ex-4 prevents this effect.

Abstract 235: Hypoxia Enhanced Delivery of Mitochondria-Targeted Catalase Protects Choroid Retinal Microvascular Endothelial Cells from Oxidative Stress

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christopher J Dougherty ◽  
Howard Prentice ◽  
Kathleen Dorey ◽  
Keith A Webster ◽  
Janet C Blanks
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Endothelial Permeability ◽  
Luciferase Assay ◽  
Expression Vectors ◽  
Microvascular Endothelial Cells ◽  
Tissue Specific ◽  
Microvascular Endothelial

Loss of pericytes is a critical event early in the progression of microvascular dysfunction in diabetic retinopathy. Pericyte loss may be linked to high glucose mediated reactive oxygen species generation, blocking N-cadherin trafficking to the endothelial cell surface preventing pericyte recruitment and vessel stabilization. Hydrogen peroxide has been identified as a major free radical produced during high glucose exposure in endothelial cells. The goal of this research is to determine if tissue-specific hypoxia-regulated expression of a mitochondria-targeted catalase can prevent or limit RF/6A microvascular endothelial cell apoptosis and decrease vascular permeability by limiting cellular oxidative stress. For the development of tissue-specific and hypoxia-enhanced expression vectors, promoters were constructed with nine tandem combinations of HREs. This 9x HRE oligomer enhancer was inserted together into a pGL3 firefly luciferase plasmid with the Tie2( short ) promoter for endothelial-specific expression. The 9xHRE-Tie2( sh ) promoter construct was highly selective for RF/6A cells producing a basal amount of mitochondria-targeted catalase equivalent to the Tie2( short ) promoter alone. In response to hypoxia ( pO 2 = 1% ), the 9xHRE-Tie2( short ) promoter showed a 21-fold hypoxia-inducible activation similar in strength to the CMV promoter , measured by dual luciferase assay. The hybrid promoters were incorporated into a replication deficient AAV delivery system for apoptosis and cell culture based endothelial permeability assays. In preliminary assays using RF/6A microvascular endothelial cells, apoptosis was reduced by 58% and permeability was reduced by 46%. The results suggest that mitochondria-targeted catalase protects RF/6A microvascular endothelial cells from apoptosis and reduces endothelial permeability in a high-glucose, low-oxygen environment.

scholarly journals Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress

2019 ◽  
Vol 8 (6) ◽  
pp. 918-927 ◽  
Author(s):  
Li Pang ◽  
Ping Deng ◽  
Yi-dan Liang ◽  
Jing-yu Qian ◽  
Li-Chuan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lipoic Acid ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Migration Ability ◽  
Microvascular Endothelial

Abstract Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

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