Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism.

Abstract

Protectin DX (PDX), which is a novel regulator of 5' adenosine monophosphate-activated protein kinase (AMPK), has recently gained attention for its ability to improve several metabolic diseases. However, the function of PDX in vascular endothelial cells remains unclear. To confirm the protective effects of PDX on endothelial oxidative stress, human umbilical vein endothelial cells (HUVECs) were treated with hydroperoxide (H2O2) and PDX. PDX treatment significantly increased the level of AMPK phosphorylation, and this elevation was attenuated after treatment with G-protein coupled receptor 120 (GPR120) antagonist or GPR120 knockdown. Expressions and activities of antioxidant proteins, including catalase and superoxide dismutase 2 (SOD2), were elevated by PDX and were inhibited by treatment with AMPK inhibitor or with GPR120 antagonist. Production of H2O2-induced reactive oxygen species (ROS), the Bax/Bcl-2 ratio, and the loss of mitochondrial membrane potential were all reversed by PDX, leading to improved cell viability and reduced release of lactate dehydrogenase (LDH). Using flow cytometry, we also found that PDX significantly reduced the H2O2-induced apoptotic population of cells. These protective effects of PDX were all reversed after treatment with AMPK inhibitor or GRP120 antagonist. These results show that the PDX-AMPK axis has a protective role against H2O2-induced oxidative stress in vascular endothelial cells.

• Authors: Hwan-Jin Hwang, Tae Woo Jung, Joo Won Kim, Jung A Kim, You Bin Lee, So Hyeon Hong, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
• Journal: Cellular signalling (Cell Signal) Vol. 53 Pg. 14-21 (01 2019) ISSN: 1873-3913 [Electronic] England
• PMID: 30244170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• 10,17-dihydroxydocosa-4,7,11,13,15,19-hexaenoic acid
• Antioxidants
• Docosahexaenoic Acids
• Hydrogen Peroxide
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Docosahexaenoic Acids (pharmacology)
• Endothelial Cells (drug effects, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hydrogen Peroxide (metabolism)
• Oxidative Stress (drug effects)