Expression of cell cycle regulatory proteins during experimental acute pancreatitis.

VACCARO, M. I.; ALEJANDRO JAVIER ROPOLO; GRASSO, D.; LANOSA, G.; IOVANNA, J. L.

Chicago, IL, USA.

Congreso; Joint Meeting of the American Pancreatic Association and the International Association of Pancreatology; 2000

American Pancreatic Association and the International Association of Pancreatology

The components of the cell cycle machinery is comprised of different protein families which are in turn responsible for the regulated progression of cells through the cell cycle. We study the expression of several cell cycle regulatory proteins during pancreatic stress induced by cerulein pancreatitis. Male Swiss mice weighing from 20 to 25 g was injected intraperitoneally 7 times with 50 mg caerulein/kg body weight with 1 hour interval. Animas (3 per group) were killed by decapitation and the pancreas were removed 0, 6, 9, 12, 18, 24 and 36 hours after cerulein first injection. P53, p21, p27, retinoblastoma protein (Rb) and cyclin dependent protein kinase 4 (Cdk4) was examined by Western blot assay. P53 increased above baseline 6 hours after cerulein first injection, its levels dropped after 12 h and remained significantly decreased afterwards. P21, gene activated by p53, and p27 showed the same time-course behavior, decreasing after 12 h of pancreatitis. Therefore, Cdk4 levels significantly rose 18 hours after cerulein treatment. Furthermore, no significative changes was observed in Rb expression during the experiment. Our results indicate that, in response to stress, during the acute phase of pancreatitis, p53 accumulates in the cell halting the cell-cycle control system in G1. From 12 h on, pancreatic cells are devoid of cell cycle inhibitors and activate the machinery to cell cycle progression increasing Cdk4. This cyclin kinase inhibits the action of Rb by phosphorilation and eventually allows the cell past the G1 checkpoint leading to DNA replication. Coordinate changes in the expression of the cell cycle proteins may trigger pancreatic regeneration early during the course of acute pancreatitis.