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Ochratoxin A induces reprogramming of glucose metabolism by switching energy metabolism from oxidative phosphorylation to glycolysis in human gastric epithelium GES-1 cells in vitro.

Authors
  • Wang, Yuan1
  • Zhao, Man2
  • Cui, Jinfeng1
  • Wu, Xin3
  • Li, Yuehong1
  • Wu, Wenxin1
  • Zhang, Xianghong4
  • 1 Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China. , (China)
  • 2 Metabolic Disease and Cancer Research Center, Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China. , (China)
  • 3 Department of Pathology, Hebei North University, Zhangjiakou, China. , (China)
  • 4 Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China; Metabolic Disease and Cancer Research Center, Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Toxicology letters
Publication Date
Aug 22, 2020
Volume
333
Pages
232–241
Identifiers
DOI: 10.1016/j.toxlet.2020.08.008
PMID: 32835834
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic and immunotoxic effects. We previously demonstrated that OTA could cause mitochondrial function disturbance in GES-1 cells in vitro, which lead to the presumption that the glucose metabolism of GES-1 cells will be altered by OTA. Therefore in the present study, we explored the toxicity of OTA on glucose metabolism of GES-1 cells and the molecular mechanism. We found that OTA could induce aerobic glycolysis, evidenced shown by increase of glucose consumption, lactate production and cellular ATP concentration. We further detected expressions of GLUT1 and glycolytic enzymes including HK2, PFK1, PKM2 and LDHA as well as tricarboxylic acid (TCA) cycle-associated enzymes including IDH1, OGDH and CS. The results showed that expression of GLUT1 as well as the activities and expressions of HK2, PFK1 and LDHA were significantly increased while IDH1 and OGDH were reduced by OTA. As to PKM2, western blot showed that OTA could elevated the phospho-PKM2 Ser37 protein level and induce the nuclear accumulation of PKM2, which was further supported by immunofluorescence analyses, in addition, pyruvate kinase activity was reduced by OTA. In conclusion, these findings suggest that OTA exposure induces the metabolic shift from oxidative phosphorylation to aerobic glycolysis via regulating the activities and expressions of glycolysis and TCA-cycle associated molecules in GES-1 cells. Copyright © 2020 Elsevier B.V. All rights reserved.

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