Developing a Model to Screen for Small Molecule Treatments that Reduce Advanced Glycation End Products Using C. elegans
Cindy Voisine is the faculty sponsor of this poster.
Abstract
Prostate cancer is the second leading cause of cancer death among men in the United States. Race and ethnicity significantly influence prostate cancer incidence and its level of aggressiveness. Recent studies have found that advanced glycation end products (AGEs) are elevated in the serum of African American compared to European American men. AGEs are harmful compounds that form when glucose covalently attaches to proteins, lipids or nucleic acids in a non-enzymatic reaction. Failure by protective cellular pathways leads to AGE accumulation and this accumulation may serves as a potential biomarker for aggressive forms of Prostate Cancer. Since the model organism Caenorhabditis elegans shares conserved components of AGE detoxification pathways that reduce AGE levels, we are developing a high throughput screen to identify small molecules that reduce AGE accumulation in the nematode. Our first objective was to induce rapid accumulation of AGEs by feeding the animals a high glucose diet and adding exogenous methylglyoxal, a precursor to AGE formation. We then monitored AGE accumulation using a green fluorescent protein (GFP) reporter, where an increase in fluorescence reflects an increase in the level of AGEs. Preliminary results suggest that a 2% glucose diet and an exogenous treatment with a high concentration of methylglyoxal (7mM) for 6 hours increase fluorescence. This breakthrough in our research gives way for high throughput assays to test for drug candidates that reduce AGEs. Our long term goal is to use C. elegans to assist in our understanding of underlying cellular mechanisms that contribute to prostate cancer disparities.
Developing a Model to Screen for Small Molecule Treatments that Reduce Advanced Glycation End Products Using C. elegans
Prostate cancer is the second leading cause of cancer death among men in the United States. Race and ethnicity significantly influence prostate cancer incidence and its level of aggressiveness. Recent studies have found that advanced glycation end products (AGEs) are elevated in the serum of African American compared to European American men. AGEs are harmful compounds that form when glucose covalently attaches to proteins, lipids or nucleic acids in a non-enzymatic reaction. Failure by protective cellular pathways leads to AGE accumulation and this accumulation may serves as a potential biomarker for aggressive forms of Prostate Cancer. Since the model organism Caenorhabditis elegans shares conserved components of AGE detoxification pathways that reduce AGE levels, we are developing a high throughput screen to identify small molecules that reduce AGE accumulation in the nematode. Our first objective was to induce rapid accumulation of AGEs by feeding the animals a high glucose diet and adding exogenous methylglyoxal, a precursor to AGE formation. We then monitored AGE accumulation using a green fluorescent protein (GFP) reporter, where an increase in fluorescence reflects an increase in the level of AGEs. Preliminary results suggest that a 2% glucose diet and an exogenous treatment with a high concentration of methylglyoxal (7mM) for 6 hours increase fluorescence. This breakthrough in our research gives way for high throughput assays to test for drug candidates that reduce AGEs. Our long term goal is to use C. elegans to assist in our understanding of underlying cellular mechanisms that contribute to prostate cancer disparities.