Journal of Gastroenterology

, Volume 45, Issue 6, pp 646–655

The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity

  • Jun-ichi Takino
  • Yuka Kobayashi
  • Masayoshi Takeuchi
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-009-0193-9

Cite this article as:
Takino, Ji., Kobayashi, Y. & Takeuchi, M. J Gastroenterol (2010) 45: 646. doi:10.1007/s00535-009-0193-9



Nonalcoholic steatohepatitis (NASH) is a feature of metabolic syndrome. Advanced glycation end-products (AGEs) are formed by the Maillard reaction, which contributes to aging and to certain pathological complications of diabetes. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs) are elevated in the sera of patients with NASH. Furthermore, immunohistochemistry of Glycer-AGEs showed intense staining in the livers of patients with NASH. The present study aimed to examine the effect of intracellular Glycer-AGEs on hepatocellular carcinoma (Hep3B) cells.


Cell viability was determined by the WST-1 assay. The slot blot and Western blot were used to detect intracellular Glycer-AGEs, and their localization was analyzed by confocal microscopy. Real-time reverse transcription-polymerase chain reaction was used to quantify the mRNA for the acute phase reactant C-reactive protein (CRP).


Glyceraldehyde (GA), which is the precursor of Glycer-AGEs, induced a concentration- and time-dependent increase in cell death, which was associated with an increase in intracellular Glycer-AGEs formation. Aminoguanidine (AG), which prevents AGEs formation, inhibited the formation of intracellular Glycer-AGEs and prevented cell death. Among the intracellular Glycer-AGEs that were formed, heat shock cognate 70 (Hsc70) was identified as a GA-modified protein, and its modification reduced the activity of Hsc70. Furthermore, intracellular Glycer-AGEs increased the CRP mRNA concentration.


These results suggest that intracellular Glycer-AGEs play important roles in promoting inflammation and hepatocellular death.


Advanced glycation end-productsGlyceraldehydeHeat shock cognate 70InflammationNonalcoholic steatohepatitis

Copyright information

© Springer 2010

Authors and Affiliations

  • Jun-ichi Takino
    • 1
  • Yuka Kobayashi
    • 1
  • Masayoshi Takeuchi
    • 1
  1. 1.Department of Pathophysiological Science, Faculty of Pharmaceutical SciencesHokuriku UniversityKanazawaJapan