Changes in the expression and dynamics of SHP-1 and SHP-2 during cerulein-induced acute pancreatitis in rats
| Autor: | Nancy Sarmiento, Nieves Pérez, Carmen Sánchez-Bernal, Jesús Sánchez-Yagüe, José Julián Calvo, Manuel Ayra, Angel Hernández-Hernández |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty animal structures MAP Kinase Kinase 4 Neutrophils chemical and pharmacologic phenomena Protein tyrosine phosphatase Mitochondrion Biology Cerulein Internal medicine medicine Extracellular Animals Rats Wistar Molecular Biology Rolipram Anthracenes SP600125 Messenger RNA Mitogen-Activated Protein Kinase 3 Kinase Protein Tyrosine Phosphatase Non-Receptor Type 6 Phosphodiesterase hemic and immune systems Acute pancreatitis Rats Endocrinology Pancreatitis SHP-2 embryonic structures SHP-1 Molecular Medicine Phosphodiesterase 4 Inhibitors biological phenomena cell phenomena and immunity Ceruletide Intracellular medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1782(4):271-279 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2008.01.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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