Salivary secretion of chromogranin A-derived peptides from irradiated patients

The secretory proteins of mammalian salivary glands are mainly synthesized and stored in secretory granules in acinar cells and released by exocytosis into saliva via beta-adrenergic receptor activation. Chromogranin A (CGA) is the major member of a family of chromogranins, markers of various diseases such as tumours and neurodegenerative pathologies, which are co-stored and co-released with adrenaline and noradrenaline in secretory chromaffin vesicles of adrenal medulla. These ubiquitous proteins are present in nervous, endocrine and immune cells, showing a predominant role in response to stress. Since several years our group has established that these proteins are processed generating numerous peptides with various biological activities. Several CGA-derived peptides display potent antibacterial and antifungal activities at the micromolar range. Objectives: the main objectives of this study were to show the implication of CGA-derived fragments in the innate defence molecules from the saliva of irradiated patients, often suffering of oral candidosis, versus the saliva from healthy controls. Methods: we have analyzed the presence of CGA-derived fragments with the proteic material extracted from the saliva of 2 patients and 1 control using gel electrophoresis, western blot with specific antibody, chromatography and proteomic techniques. Results: the pathophysiological state of the patient is confirmed by proteomic analysis and we have shown an over expression of CGA and several derived peptides in the saliva from patients by comparison with controls. These data are related with the antimicrobial activities of these natural fragments. Conclusions: we have shown that for the first time using very sensitive biochemical methods we have shown that saliva from irradiated patients contains antimicrobial fragments derived from CGA.