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Glyceraldehyde-3-Phosphate, a Glycolytic Intermediate, Plays a Key Role in Controlling Cell Fate Via Inhibition of Caspase Activity

  • Jang, Mi (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Hyo Jin (BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Sun Young (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Chung, Sang J. (BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Sunghyun (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Chi, Seung Wook (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Sayeon (College of Pharmacy, Chung-Ang University) ;
  • Lee, Sang Chul (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Chong-Kil (Department of Pharmacy, Chungbuk National University) ;
  • Park, Byoung Chul (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Bae, Kwang-Hee (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Sung Goo (Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2009.08.19
  • Accepted : 2009.09.17
  • Published : 2009.12.31

Abstract

Glyceraldehyde-3-phosphate is a key intermediate in several central metabolic pathways of all organisms. Aldolase and glyceraldehyde-3-phosphate dehydrogenase are involved in the production or elimination of glyceraldehyde-3-phosphate during glycolysis or gluconeogenesis, and are differentially expressed under various physiological conditions, including cancer, hypoxia, and apoptosis. In this study, we examine the effects of glyceraldehyde-3-phosphate on cell survival and apoptosis. Overexpression of aldolase protected cells against apoptosis, and addition of glyceraldehyde-3-phosphate to cells delayed apoptosis. Additionally, delayed apoptotic phenomena were observed when glyceraldehyde-3-phosphate was added to a cell-free system, in which artificial apoptotic process was induced by adding dATP and cytochrome c. Surprisingly, glyceraldehyde-3-phosphate directly suppressed caspase-3 activity in a reversible noncompetitive mode, preventing caspase-dependent proteolysis. Based on these results, we suggest that glyceraldehyde-3-phosphate, a key molecule in several central metabolic pathways, functions as a molecule switch between cell survival and apoptosis.

Keywords

Acknowledgement

Supported by : Korea Research Institute of Bioscience and Biotechnology, National Research Foundation of Korea, Korea Science and Engineering Foundation

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