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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalCellular Signalling
Volume53
DOIs
Publication statusPublished - 2019 Jan 1

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Adenosine Monophosphate
Protein Kinases
Oxidative Stress
Endothelial Cells
G-Protein-Coupled Receptors
Protein Kinase Inhibitors
10,17-dihydroxydocosa-4,7,11,13,15,19-hexaenoic acid
Mitochondrial Membrane Potential
Metabolic Diseases
Human Umbilical Vein Endothelial Cells
L-Lactate Dehydrogenase
Catalase
Hydrogen Peroxide
Reactive Oxygen Species
Cell Survival
Flow Cytometry
Antioxidants
Phosphorylation

Keywords

  • Apoptosis
  • Endothelial cells
  • Oxidative stress
  • Protectin DX

ASJC Scopus subject areas

  • Cell Biology

Cite this

Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism. / Hwang, Hwan Jin; Jung, Tae Woo; Kim, Joo Won; Kim, Jung A.; Lee, You Bin; Hong, So Hyeon; Roh, Eun; Choi, Kyung Mook; Baik, Sei-Hyun; Yoo, Hye-Jin.

In: Cellular Signalling, Vol. 53, 01.01.2019, p. 14-21.

Research output: Contribution to journalArticle

Hwang, Hwan Jin ; Jung, Tae Woo ; Kim, Joo Won ; Kim, Jung A. ; Lee, You Bin ; Hong, So Hyeon ; Roh, Eun ; Choi, Kyung Mook ; Baik, Sei-Hyun ; Yoo, Hye-Jin. / Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism. In: Cellular Signalling. 2019 ; Vol. 53. pp. 14-21.
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