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

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Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism.
Cellular Signalling ( IF 4.4 ) Pub Date : 2018-09-20 , DOI: 10.1016/j.cellsig.2018.09.011
Hwan-Jin Hwang ₁ , Tae Woo Jung ₁ , Joo Won Kim ₁ , Jung A Kim ₁ , You Bin Lee ₁ , So Hyeon Hong ₁ , Eun Roh ₁ , Kyung Mook Choi ₁ , Sei Hyun Baik ₁ , Hye Jin Yoo ₁

Affiliation

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.

中文翻译：

Protectin DX通过AMPK依赖性机制防止H2O2介导的血管内皮细胞氧化应激。

Protectin DX（PDX）是5'腺苷单磷酸激活蛋白激酶（AMPK）的新型调节剂，最近因其改善几种代谢性疾病的能力而受到关注。然而，PDX在血管内皮细胞中的功能仍不清楚。为了证实PDX对内皮氧化应激的保护作用，用过氧化氢（H2O2）和PDX处理了人脐静脉内皮细胞（HUVEC）。PDX处理显着提高了AMPK磷酸化水平，在使用G蛋白偶联受体120（GPR120）拮抗剂或GPR120敲低后，这种升高减弱。PDX可提高抗氧化蛋白（包括过氧化氢酶和超氧化物歧化酶2（SOD2））的表达和活性，并被AMPK抑制剂或GPR120拮抗剂抑制。PDX可以逆转H2O2诱导的活性氧（ROS）的产生，Bax / Bcl-2的比率以及线粒体膜电位的丧失，从而改善细胞活力并减少乳酸脱氢酶（LDH）的释放。使用流式细胞仪，我们还发现PDX显着减少了H2O2诱导的细胞凋亡。用AMPK抑制剂或GRP120拮抗剂治疗后，PDX的这些保护作用均被逆转。这些结果表明，PDX-AMPK轴对H2O2诱导的血管内皮细胞氧化应激具有保护作用。我们还发现PDX显着降低了H2O2诱导的细胞凋亡。用AMPK抑制剂或GRP120拮抗剂治疗后，PDX的这些保护作用均被逆转。这些结果表明，PDX-AMPK轴对H2O2诱导的血管内皮细胞氧化应激具有保护作用。我们还发现PDX显着降低了H2O2诱导的细胞凋亡。用AMPK抑制剂或GRP120拮抗剂治疗后，PDX的这些保护作用均被逆转。这些结果表明，PDX-AMPK轴对H2O2诱导的血管内皮细胞氧化应激具有保护作用。

更新日期：2018-09-20

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