Objective: The objective of this study was to determine the effects of fructose and their advanced glycation end products (fru-AGES) on histone acetylation in microglia, the immune cells of the brain.
Significance: Fru-AGES primarily form as a result of non-enzymatic reactions between fructose and proteins. One result is inflammation in the brain, which can be directly correlated to increased microglia activity. Microglial activity has been shown to be associated with the acetylation of histones, resulting in a change in transcription of inflammatory genes. Elucidation of a direct link between fructose, fru-AGES and histone acetylation would increase understanding the pathophysiology of inflammatory disorders such as Alzheimer’s disease.
Experimental Procedures: An immortalized rat microglial cell line was treated in vitro with control media, fru-AGES or fructose. Histone acetylation was analyzed indirectly through activity of histone deacetlyase (HDAC) using the HDAC Glo I/II Assay (Promega). Chemiluminescent product formation was measuring with a spectrophotometer.
Results Obtained: Both treatments with fructose and fru-AGES showed an increase in HDAC activity compared to control by up to 35% and 20%, respectively, correlating to a decrease in global histone acetylation. This is contradictory to initial expectations, as a decrease in acetylation could result in a decrease in transcription of genes . Despite causing an initial inflammatory response, fructose and fru-AGES appear to suppress overall gene transcription.
Conclusion: Previous data show that exposure of microglia to fructose and fru-AGES results in a pro-inflammatory activated state. However, at the level of gene transcription, microglia may be desensitized and less able to respond in the long term.
Cornacchia, Alissa K.; Hall, MacKenzie; and Lull, Melinda E., "Effects of Fructose-Derived Advanced Glycation End Products on Acetylation of Histones in the Brain" (2015). Undergraduate External Publications. Paper 5.
Please note that the Publication Information provides general citation information and may not be appropriate for your discipline. To receive help in creating a citation based on your discipline, please visit http://libguides.sjfc.edu/citations.