Modulation in the expression of SHP-1, SHP-2 and PTP1B due to the inhibition of MAPKs, cAMP and neutrophils early on in the development of cerulein-induced acute pancreatitis in rats

Autor: Violeta García-Hernández, Carmen Sánchez-Bernal, Laura Pascual Matellán, Nancy Sarmiento, José Julián Calvo, Jesús Sánchez-Yagüe
Rok vydání: 2014
Předmět:
Male
MAPK/ERK pathway
medicine.medical_specialty
Time Factors
Infiltration inhibition
p38 mitogen-activated protein kinases
Immunoblotting
Regulator
Protein Tyrosine Phosphatase
Non-Receptor Type 11
Protein tyrosine phosphatase
Internal medicine
White blood cell
Cyclic AMP
medicine
Extracellular
Animals
Rats
Wistar
Pancreas
Experimental acute pancreatitis
Molecular Biology
Anthracenes
Flavonoids
Mitogen-Activated Protein Kinase 1
Protein Tyrosine Phosphatase
Non-Receptor Type 1
Mitogen-Activated Protein Kinase 3
Kinase
Chemistry
Protein Tyrosine Phosphatase
Non-Receptor Type 6
JNK Mitogen-Activated Protein Kinases
PTP1B
Immunohistochemistry
Rats
Cell biology
MAPK inhibition
Endocrinology
medicine.anatomical_structure
Neutrophil Infiltration
Pancreatitis
Acute Disease
SHP-2
SHP-1
Molecular Medicine
Mitogen-Activated Protein Kinases
Ceruletide
Intracellular
Zdroj: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1842(2):192-201
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2013.11.003
Popis: The protein tyrosine phosphatases (PTPs) SHP-1, SHP-2 and PTP1B are overexpressed early on during the development of cerulein -induced acute pancreatitis (AP) in rats, and their levels can be modulated by some species of mitogen-activated protein kinases (MAPKs), the intracellular levels of cAMP and by general leukocyte infiltration, the latter at least for SHP-2 and PTP1B. In this study we show that cerulein treatment activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) but not p38 MAPK during the early phase of cerulein-induced AP (2h after the first injection of cerulein). Therefore, by using the MAPK inhibitors SP600125 (a specific JNK inhibitor) and PD98059 (a specific ERK inhibitor), we have unmasked the particular MAPK that underlies the modulation of the expression levels of these PTPs. JNK would act by preventing SHP-1 protein expression from increasing beyond a certain level. ERK 1/2 was the main MAPK involved in the increase in SHP-2 protein expression due to cerulein. JNK negatively modulated the SH2-domain containing PTPs. Both MAPKs played a role in the increase in PTP1B protein expression due to cerulein. Finally, by using the white blood cell inhibitors vinblastine sulfate, gadolinium chloride and FK506 (tacrolimus), we show that the macrophage activity or T-lymphocytes does not modulate the expression of any of the PTPs, although neutrophil infiltration was found to be a regulator of SHP-2 and PTP1B protein expression due to cerulein.
Databáze: OpenAIRE
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