MDH1 and MDH2 Promote Cell Viability of Primary AT2 Cells by Increasing Glucose Uptake

Abstract

Background. Acute lung injury (ALI) is a clinical disease with high morbidity and mortality, with limited treatment means. For primary alveolar epithelial type II (AT2) cells, glycolysis is an essential bioenergetic process. However, the significance of AT2 cell glycolysis in sepsis ALI remains unknown. Methods and Results. In the current study, based on microarray analysis, real-time quantitative PCR, and Western blotting, we found that the hsa00020: citrate cycle pathway was inactivated, specifically its downstream gene: malate dehydrogenase 1 (MDH1) and MDH2 in ALI. In this context, lipopolysaccharides (LPS) were used to construct the septic-ALI mouse model and the biological function of MDH1 and MDH2 in primary alveolar epithelial type II (AT2) cells was explored. Through CCK-8, EdU, transwell, and apoptosis assays, we found that MDH1 and MDH2 promoted the cell vitality of AT2 cells, which relied on MDH1 and MDH2 to promote the glucose intake of AT2 cells. Conclusion. Overall, these findings suggest that targeting MDH1/MDH2-mediated AT2 cell glycolysis may be a potential strategy for ALI patients.

The acetylation of MDH1 and IDH1 is associated with energy metabolism in acute liver failure

“…MDH1 can promote the viability of alveolar epithelial type II cells by promoting glucose intake, suggesting that targeting MDH1 may be a potential therapeutic strategy for patients with acute lung injury. 12 In addition, the MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells. 13 Recent studies have shown that MDH1 can regulate autophagy and is required to maintain the level of the autophagy promoter unc-51 like autophagy activating kinase 1 (ULK1), and the activity of MDH1 increases after autophagy induction.…”

Design, Synthesis and Biological Evaluation of Novel MDH Inhibitors Targeting Tumor Microenvironment

“…The expression levels of MDH1 and MDH2 are high in patients with lung cancer [ 4 , 10 ]. High expression of MDH1 is significantly correlated with patient survival, and its knockdown affects cell viability compared with that of MDH2 [ 10 , 11 ]. A previous report presented LW1497 , a dual inhibitor of MDH1 and MDH2, which showed significant in vivo antitumor effects against colon cancer through the inhibition of mitochondrial respiration and hypoxia-inducible factor-1 alpha (HIF-1α) accumulation [ 12 , 13 ].…”

Retracted: MDH1 and MDH2 Promote Cell Viability of Primary AT2 Cells by Increasing Glucose Uptake

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”