HIF1α-Induced Glycolysis in Macrophage Is Essential for the Protective Effect of Ouabain during Endotoxemia. (28th April 2019)

• Record Type: Journal Article
• Authors: Shao, Chao; Lin, Shengwei; Liu, Sudan; Jin, Peipei; Lu, Wenbin; Li, Na; Zhang, Yan; Bo, Lulong; Bian, Jinjun
• Other Names: Collino Massimo Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2019(2019)
• Publication Date: 2019-04-28
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2019/7136585
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Ouabain, a steroid binding to the Na + /K + -ATPase, has several pharmacological effects. In addition to the recognized effects of blood pressure, there is more convincing evidence suggesting that ouabain is involved in immunologic functions and inflammation. Hypoxia-inducible factor 1 α (HIF-1 α ) is a metabolic regulator which plays a considerable role in immune responses. Previous studies had shown that HIF-1 α -induced glycolysis results in functional reshaping in macrophages. In this study, we investigated the role of glycolytic pathway activation in the anti-inflammatory effect of ouabain. We found that ouabain is involved in anti-inflammatory effects both in vivo and in vitro. Additionally, ouabain can inhibit LPS-induced upregulation of GLUT1 and HK2 at the transcriptional level. GM-CSF pretreatment almost completely reversed the inhibitory effect of ouabain on LPS-induced release of proinflammatory cytokines. Alterations in glycolytic pathway activation were required for the anti-inflammatory effect of ouabain. Ouabain can significantly inhibit the upregulation of HIF-1 α at the protein level. Our results also revealed that the overexpression of HIF-1 α can reverse the anti-inflammatory effect of ouabain. Thus, we conclude that the HIF-1 α -dependent glycolytic pathway is essential for the anti-inflammatory effect of ouabain.