P67 Slow release H2S donors protect human microvascular endothelial cells from oxidative stress induced cell death: Markedly increased potency by mitochondria-targeting

Nitric Oxide ◽  
2012 ◽  
Vol 27 ◽  
pp. S40-S41
Author(s):  
Sophie Le Trionnaire ◽  
Jackie Whatmore ◽  
Alexis Perry ◽  
Mark E Wood ◽  
Whiteman Matthew
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Death ◽  
Slow Release ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Mitochondria Targeting

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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