Suppression of Apoptosis in Salivary Acinar Cells Isolated from Transgenic Mice Expressing Constitutively Activated Akt

Tissue homeostasis and physiological function of organs rely on the balance of cell proliferation and cell death. Recent years evidence has suggested that the phosphatidylinositol 3’-kinase/Akt pathway plays an important role in regulation of cell size as well as programmed cell death. Methods: We have recently generated transgenic mice in which expression of a constitutively activated mutant of Akt1, myr-Akt1, was expressed in the salivary glands. Transgene expression profiles revealed significant levels of myr-Akt1 in three major salivary glands (submandibular, sublingual, and parotid) at four weeks of age and continued through adulthood (> 6 months). Objective: The effect of transgene expression in salivary acinar cells was characterized by examining the physiology of the glands and the biology of these cells after an apoptotic insult. Results: We report that expression of the myr-Akt1 transgene did not drastically alter the cellularity or physiologic function of the salivary glands; there is no change salivary output and the protein composition of saliva is not altered in transgenic mice when compared to normal control mice. Transgene expression did slightly alter cellular size and significantly altered the response of primary salivary acinar cells prepared from these mice to an apoptotic insult. The response of primary acinar cells isolated from myr-Akt1 transgenic mice to apoptotic stimuli such as etoposide, brefeldin A, and g-irradiation was significantly decreased when compared to acinar cells isolated from FVB control mice. Conclusion: Akt activation may have the potential to temporarily suppress the inadvertent apoptosis in salivary glands that occurs secondary to irradiation of the head and neck, or other chemotherapeutic treatments. This work has been supported in part by: PO1 DE12798, the Sjögren’s Syndrome Foundation and NRSA DE14315.