Category
Applied
Description
Gastric disorders, such as gastroesophageal reflux disease (GERD) affect at least 20% of the United States population. The most common pharmacological intervention is the use of Proton Pump Inhibitors (PPIs). These drugs are converted into their active forms upon entry into acidic environments, and while their intended function is to inhibit parietal proton pumps in the stomach and reduce gastric acid secretion, there may be off-target effects in other areas with low pH, such as lysosomes. These organelles mediate the recycling and degradation of cellular materials. The current research seeks to examine the effect of PPIs on lysosomal function. Previous scientific studies have shown that PPIs such as lansoprazole and omeprazole can inhibit lysosomal enzyme activity. Decreased lysosomal activity has been implicated in impaired immune function and the development of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other diseases.
Preliminary experimental results demonstrate the successful isolation of active lysosomes from multiple murine tissue types including brain, liver, lung, kidney, and spleen. Lysosomes were also extracted from cultured cell lines, specifically COS-1 cells derived from monkey kidneys. These lysosomal fractions were obtained via differential centrifugation, and their activity was confirmed using an acid phosphatase assay, the standard method for assessing lysosomal function. Finally, COS-1 cells were treated with PPIs, and the lysosome activity was measured, clearly demonstrating altered enzymatic function due to the presence of the PPI. Future experiments will extend this analysis by testing the effects of PPIs on another lysosomal enzyme, ß-N-acetylglucosaminidase (ß-NAG), and on other cell lines, such as Caco-2 and A549 cells. This experimental procedure also allowed for the examination of the effects of additional compounds, including natural products and food additives, on proton pumps and overall lysosomal function.
The Effects of Natural Products and Food Additives on Lysosome Function
Applied
Gastric disorders, such as gastroesophageal reflux disease (GERD) affect at least 20% of the United States population. The most common pharmacological intervention is the use of Proton Pump Inhibitors (PPIs). These drugs are converted into their active forms upon entry into acidic environments, and while their intended function is to inhibit parietal proton pumps in the stomach and reduce gastric acid secretion, there may be off-target effects in other areas with low pH, such as lysosomes. These organelles mediate the recycling and degradation of cellular materials. The current research seeks to examine the effect of PPIs on lysosomal function. Previous scientific studies have shown that PPIs such as lansoprazole and omeprazole can inhibit lysosomal enzyme activity. Decreased lysosomal activity has been implicated in impaired immune function and the development of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other diseases.
Preliminary experimental results demonstrate the successful isolation of active lysosomes from multiple murine tissue types including brain, liver, lung, kidney, and spleen. Lysosomes were also extracted from cultured cell lines, specifically COS-1 cells derived from monkey kidneys. These lysosomal fractions were obtained via differential centrifugation, and their activity was confirmed using an acid phosphatase assay, the standard method for assessing lysosomal function. Finally, COS-1 cells were treated with PPIs, and the lysosome activity was measured, clearly demonstrating altered enzymatic function due to the presence of the PPI. Future experiments will extend this analysis by testing the effects of PPIs on another lysosomal enzyme, ß-N-acetylglucosaminidase (ß-NAG), and on other cell lines, such as Caco-2 and A549 cells. This experimental procedure also allowed for the examination of the effects of additional compounds, including natural products and food additives, on proton pumps and overall lysosomal function.
