Cellular physiology and biochemistry, 2017-01, Vol.41 (2), p.623-634
2017
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- P38 MAPK Pharmacological Inhibitor SB203580 Alleviates Total Parenteral Nutrition-Induced Loss of Intestinal Barrier Function but Promotes Hepatocyte Lipoapoptosis
- Ist Teil von
- Cellular physiology and biochemistry, 2017-01, Vol.41 (2), p.623-634
- Ort / Verlag
- Basel, Switzerland: S. Karger AG
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background & Aims: Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. Methods: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications.Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining. Results: In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1β-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment. Conclusions: We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1015-8987eISSN: 1421-9778DOI: 10.1159/000457933Titel-ID: cdi_pubmed_primary_28214831
- Format
- –
- Schlagworte
- Activating Transcription Factor 2 - antagonists & inhibitors, Activating Transcription Factor 2 - genetics, Activating Transcription Factor 2 - metabolism, Animals, Apoptosis - drug effects, Caco-2 Cells, Caspase 3 - metabolism, Caspase 7 - metabolism, Hepatocytes - cytology, Hepatocytes - drug effects, Hepatocytes - metabolism, Humans, Imidazoles - pharmacology, Interleukin-1beta - pharmacology, Intestinal barrier, Intestinal Mucosa - drug effects, Intestinal Mucosa - metabolism, Kinases, Lipoapoptosis, Male, Membrane Potential, Mitochondrial - drug effects, Models, Animal, Original Paper, P38 MAPK, p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases - metabolism, Palmitic Acid - toxicity, Parenteral nutrition, Parenteral Nutrition, Total, Permeability - drug effects, Pyridines - pharmacology, Rats, Rats, Sprague-Dawley, RNA Interference, Rodents, SB203580, Small intestine, Total parenteral nutrition