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The Formation of Intracellular Glyceraldehyde-Derived Advanced Glycation End-Products and Cytotoxicity

The Formation of Intracellular Glyceraldehyde-Derived Advanced Glycation End-Products and Cytotoxicity

Jun-ichi Takino, Yuka Kobayashi, Masayoshi Takeuchi

J Gastroenterol. 2010 Jun;45(6):646-55.

PMID: 20084527

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP7325168	Glycer(ol-d3)		7325-16-8	Price

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