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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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

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Acknowledgments

This work was supported in part by grants from the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (B), #19300254).

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Authors and Affiliations

  1. Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, 920-1181, Japan

    Jun-ichi Takino, Yuka Kobayashi & Masayoshi Takeuchi

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  1. Jun-ichi Takino
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  2. Yuka Kobayashi
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  3. Masayoshi Takeuchi
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Correspondence to Masayoshi Takeuchi.

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Takino, Ji., Kobayashi, Y. & Takeuchi, M. The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity. J Gastroenterol 45, 646–655 (2010). https://doi.org/10.1007/s00535-009-0193-9

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  • DOI: https://doi.org/10.1007/s00535-009-0193-9

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