Protein Isoaspartate Methyltransferase Prevents Apoptosis Induced by Oxidative Stress in Endothelial Cells: Role of Bcl-Xl Deamidation and Methylation

Peroxiredoxin 6 (Prdx6) is a cytoprotective enzyme with largely unknown in vivo functions. Here, we use Prdx6 knockout mice to determine its role in UV protection and wound healing. UV-mediated keratinocyte apoptosis is enhanced in Prdx6-deficient mice. Upon skin injury, we observe a severe hemorrhage in the granulation tissue of knockout animals, which correlates with the extent of oxidative stress. At the ultrastructural level endothelial cells appear highly damaged, and their rate of apoptosis is enhanced. Knock-down of Prdx6 in cultured endothelial cells also increases their susceptibility to oxidative stress, thus confirming the sensitivity of this cell type to loss of Prdx6. Wound healing studies in bone marrow chimeric mice demonstrate that Prdx6-deficient inflammatory and endothelial cells contribute to the hemorrhage phenotype. These results provide insight into the cross-talk between hematopoietic and resident cells at the wound site and the role of reactive oxygen species in this interplay.

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Cytoprotection of human endothelial cells from oxidative stress by polyphenols: the role of gene expression versus direct antioxidant effect

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.760.3 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Xinyu Wang ◽

James Bynum ◽

Salomon Stavchansky ◽

Michael Dubick ◽

Robert Hackman ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Endothelial Cells ◽

Antioxidant Effect ◽

Human Endothelial Cells

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Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Cancer Research ◽

10.1158/0008-5472.can-07-3034 ◽

2007 ◽

Vol 67 (24) ◽

pp. 11906-11913 ◽

Cited By ~ 76

Author(s):

L.-F. Dong ◽

E. Swettenham ◽

J. Eliasson ◽

X.-F. Wang ◽

M. Gold ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Vitamin E ◽

Induction Of Apoptosis

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Effect of Blueberry Anthocyanins Malvidin and Glycosides on the Antioxidant Properties in Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1591803 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 31

Author(s):

Wuyang Huang ◽

Yunming Zhu ◽

Chunyang Li ◽

Zhongquan Sui ◽

Weihong Min

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endothelial Cells ◽

Functional Food ◽

Functional Role ◽

Antioxidant Properties ◽

Heme Oxygenase 1 ◽

Oxygen Species ◽

Good Resource

The objective of this research was to survey the antioxidant functional role of the main anthocyanins of blueberries in endothelial cells. Changes on the reactive oxygen species (ROS), xanthine oxidase-1 (XO-1), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) in cells of malvidin and the two glycosides were investigated. The results showed that these anthocyanins decreased the levels of ROS and XO-1 but increased the levels of SOD and HO-1. Glycosides improved the antioxidant capacity of malvidin to a great extent. The changes in the antioxidant properties of malvidin-3-glucoside were more pronounced than malvidin-3-galactoside. Variation in levels of malvidin-3-glucoside and malvidin-3-galactoside had a significant impact on antioxidant properties to different extents. It indicates that blueberries are a good resource of anthocyanins, which can protect cells from oxidative deterioration and use blueberry as a potential functional food to prevent diseases related to oxidative stress.

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Hyperketonemia (Acetoacetate) Upregulates NADPH Oxidase 4 and Elevates Oxidative Stress, ICAM-1, and Monocyte Adhesivity in Endothelial Cells

Cellular Physiology and Biochemistry ◽

10.1159/000369702 ◽

2015 ◽

Vol 35 (1) ◽

pp. 364-373 ◽

Cited By ~ 29

Author(s):

Preeti Kanikarla-Marie ◽

Sushil K. Jain

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

High Glucose ◽

Microvascular Dysfunction ◽

New Drugs ◽

Cellular Injury ◽

Nadph Oxidase 4 ◽

Antisense Approach ◽

Cellular Dysfunction

Background/Aims: The incidence of developing microvascular dysfunction is significantly higher in type 1 diabetic (T1D) patients. Hyperketonemia (acetoacetate, β-hydroxybutyrate) is frequently found along with hyperglycemia in T1D. Whether hyperketonemia per se contributes to the excess oxidative stress and cellular injury observed in T1D is not known. Methods: HUVEC were treated with ketones in the presence or absence of high glucose for 24 h. NOX4 siRNA was used to specifically knockdown NOX4 expression in HUVEC. Results: Ketones alone or in combination with high glucose treatment cause a significant increase in oxidative stress, ICAM-1, and monocyte adhesivity to HUVEC. Using an antisense approach, we show that ketone induced increases in ROS, ICAM-1 expression, and monocyte adhesion in endothelial cells were prevented in NOX4 knockdown cells. Conclusion: This study reports that elevated levels of ketones upregulate NOX, contributing to increased oxidative stress, ICAM-1 levels, and cellular dysfunction. This provides a novel biochemical mechanism that elucidates the role of hyperketonemia in the excess cellular injury in T1D. New drugs targeting inhibition of NOX seems promising in preventing higher risk of complications associated with T1D.

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