Proliferation-Apoptosis Balance in Salivary Gland Hypertrophy Models

Objectives: A close relationship has been established between cell proliferation and subsequent apoptosis. Apoptosis is initiated either by ligand binding to cell surface receptors (extrinsic pathway) or by intracellular signals via a pathway that targets the mitochondria (intrinsic pathway). The aim of the present study was to investigate whether there is an increase of apoptotic activity in the hypertrophy/hyperplasia of the rat parotid and submandibular glands, induced by the beta-agonist isoproterenol (IPR) and soya feeding (which produces enlargement of pancreas and parotid glands). We also investigated the difference in activity between the two possible apoptotic signal routes. Methods: Thirty female Wistar rats weighing 200-250g were used. One of the experimental groups was treated i.p. with 1mg/100g b.w./day IPR, the other group was feed with heat dried (100°C, 1 hour) soya bean for periods of 2, 5 and 10 days. Controls and IPR-treated animals were fed with standard rat chow. Hypertrophy was measured as tissue weight and protein content. Apoptosis was detected by caspase -3/7,-8,-9 luminescence assays from mitochondria-free supernatant of glandular tissues. Results: Both IPR-treatment and soya feed caused a continuous enlargement of parotids, about 3-fold for the 10th day. In the case of submandibular glands, enlargement was produced only by IPR. The effector caspase, the caspase-3/7 activity increased in both glands following IPR-treatment. Caspase-3/7 activity of soya fed group was increased only in the submandibular glands on the 10th day. Activity changes of caspase-8, caspase-9 were the same as on caspase-3/7. Conclusion: Our findings by IPR-treatment confirm that widely-accepted knowledge that the proliferation and apoptosis are interdependent events. This synchronism was not detected during the soya feeding. Further studies are needed to analyze the cause of the lack of induction of apoptosis and the role of the anti-apoptotic agents, inhibiting the activation of caspases. Supported by: OTKA T-046511, Hungary