title: Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats.
abstract: Protein tyrosine phosphatases (PTPs) are important regulators of cell functions but data on different PTP expression and dynamics in acute pancreatitis (AP) are very scarce. Additionally, both c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinases (ERK1/2), together with intracellular cAMP levels in inflammatory cells, play an essential role in AP. In this study we have detected an increase in PTP SHP-1 and SHP-2 in the pancreas at the level of both protein and mRNA as an early event during the development of Cerulein (Cer)-induced AP in rats. Nevertheless, while SHP-2 protein returned to baseline levels in the intermediate or later phases of AP, SHP-1 protein expression remained increased throughout the development of the disease. The increase in SHP-2 protein expression was associated with changes in its subcellular distribution, with higher percentages located in the fractions enriched in lysosomes+mitochondria or microsomes. Furthermore, while the increase in SHP-2 protein was also observed in sodium-taurocholate duct infusion or bile-pancreatic duct obstruction AP, that of SHP-1 was specific to the Cer-induced model. Neutrophil infiltration did not affect the increase in SHP-1 protein, but favoured the return of SHP-2 protein to control levels, as indicated when rats were rendered neutropenic by the administration of vinblastine sulfate. Inhibition of JNK and ERK1/2 with SP600125 pre-treatment further increased the expression of both SHP-1 and SHP-2 proteins in the early phase of Cer-induced AP, while the inhibition of type IV phosphodiesterase with rolipram only suppressed the increase in SHP-2 protein expression during the same phase. Our results show that AP is associated with increases in the expression of SHP-1 and SHP-2 and changes in the dynamics of SHP-2 subcellular distribution in the early phase of Cer-induced AP. Finally, both JNK and ERK1/2 and intracellular cAMP levels are able to modulate the expression of these PTPs.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, Spain.
authors.forename: Nancy
authors.initials: N
authors.lastname: Sarmiento
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Bernal
authors.forename: Manuel
authors.initials: M
authors.lastname: Ayra
authors.forename: Nieves
authors.initials: N
authors.lastname: Pérez
authors.forename: Angel
authors.initials: A
authors.lastname: Hernández-Hernández
authors.forename: José J
authors.initials: JJ
authors.lastname: Calvo
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez-Yagüe
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002108:Ceruletide; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000276:immunology; D010195:Pancreatitis / Q000139:chemically induced* / Q000201:enzymology*; D058988:Phosphodiesterase 4 Inhibitors; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D058988:Phosphodiesterase 4 Inhibitors; C432165:pyrazolanthrone; D002108:Ceruletide; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D020889:Rolipram