0000000000002749
AUTHOR
Natalia Sacilotto
Pentoxifylline Prevents Loss of PP2A Phosphatase Activity and Recruitment of Histone Acetyltransferases to Proinflammatory Genes in Acute Pancreatitis
Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activiti…
Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restores Gene Expression Levels.
The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These resu…
Epigenetic Transcriptional Regulation of the Growth Arrest-Specific gene 1 (Gas1) in Hepatic Cell Proliferation at Mononucleosomal Resolution
Background Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. Methodology/Principal Findings Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real …
ACTIVIDAD DE LA SER/THR FOSFATASA PP2A Y REGULACIÓN EPIGENÉTICA DE GENES PRO-INFLAMATORIOS EN LA PANCREATITIS AGUDA
Objetivos 1) Estudiar el papel de las serin/treonin protein fosfatasas en la induccion de genes pro-inflamatorios en el pancreas en la pancreatitis aguda, 2) Investigar el papel de las serin/treonin fosfatasas en el mecanismo de accion de la pentoxifilina como agente inflamatorio en la PA. Diseno Modelo de PA necrotica en ratas inducida por taurocolato sodico al 3,5%. Determinacion en pancreas de ratas de la fosforilacion de ERK y MEK1/2 (western blotting), las actividades de las serin/treonin fosfatasas PP2A, PP2B y PP2C, la induccion de genes pro-inflamatorios (RT-PCR e immunoprecipitacion de la cromatina) y el reclutamiento de factores de transcripcion e histonas acetiltransferasas/deace…