Expression and Localization of Huntingtin-Associated Protein 1 (HAP1) in the Human Digestive System

BackgroundHuntingtin-associated protein 1 (HAP1) is a neuronal protein that is predominantly expressed in neurons in the brain. HAP1 is critical for maintenance of neuronal survival as well as regulation of food intake and body weight in animals. In addition to the criticalrole of HAP1 in the central nervous system, HAP1 is also found in endocrine cells, raising an interesting issue of whether HAP1 is expressed in the digestive system.AimsTo examine the expression and localization of HAP1 in the human gastrointestinal tract and to compare the differences of the HAP1 expression between benign and malignant tissues in the digestive system.MethodsWe used Western blot and immunohistochemistry to examine the expression and distribution of HAP1 in the human gastrointestinal tract tissues.ResultsWe observed that the presence of HAP1-positive cells in the gastrointestinal tract was not uniform with immunohistochemistry staining. Western blot revealed that only one isoform (75KD) HAP1 was present in the human gastrointestinal system. Interestingly, the expression of HAP1 was higher in the stomach than other regions of the gastrointestinal tract and was at the lowest level in the intestine. We also found that HAP1 was unlikely altered in benign gastric polyps, but was downregulated in pancreatic cancer.ConclusionsThis is the first study showing the differential expression and location of HAP1 in the human digestive system. These findings suggested that HAP1 may have cell-type-dependent function in the gastrointestinal tract and may serve as a diagnostic marker for pancreatic cancer.