Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion inHelicobacter pyloriinfection
| العنوان: | Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion inHelicobacter pyloriinfection |
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| المؤلفون: | Michael Vieth, Olga Sokolova, Michael Naumann |
| المصدر: | Gut |
| بيانات النشر: | BMJ, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | MARCKS, Polymerase Chain Reaction, Cell Movement, Phosphorylation, Protein Kinase C, gastro-oesphageal junction, Aged, 80 and over, c-Fos, Gastroenterology, cell signalling, gastric pre-cancer, gastro-oesophageal reflux disease, Middle Aged, Immunohistochemistry, Up-Regulation, Isoenzymes, CagA, medicine.anatomical_structure, Biochemistry, Gastritis, helicobacter pylori—pathogenesis, PLC, Matrix Metalloproteinase 1, signal transduction, Adult, matrix metalloproteinase, mucosal pathology, gastric neoplasia, gastrointestinal cancer, Immunoblotting, Adenocarcinoma, Biology, Isozyme, Helicobacter Infections, molecular oncology, Stomach Neoplasms, inflammatory bowel disease, Gastric mucosa, medicine, Humans, nuclear factor kappa b, gastric inflammation, Protein kinase C, Aged, barretts metaplasia, Helicobacter pylori, Phospholipase C, Activator (genetics), bacterial infection, AP-1, biology.organism_classification, Molecular biology, Enzyme Activation, Transcription Factor AP-1, Gene Expression Regulation, Gastric Mucosa, inflammation, Type C Phospholipases, barretts carcinoma, Calcium, Phosphatidylinositol 3-Kinase |
| الوصف: | Background Protein kinase C (PKC) signalling is often dysregulated in gastric cancer and therefore represents a potential target in cancer therapy. The Gram-negative bacterium Helicobacter pylori , which colonises the human stomach, plays a major role in the development of gastritis, peptic ulcer and gastric adenocarcinoma. Objective To analyse the role of PKC isozymes as mediators of H pylori -induced pathogenesis. Methods PKC phosphorylation was evaluated by immunoblotting and immunohistochemistry. Gene reporter assays, RT-PCR and invasion assays were performed to assess the role of PKC in the regulation of activator protein-1 (AP-1), matrix metalloproteinase-1 (MMP-1) and the invasion of H pylori -infected epithelial cells. Results H pylori induced phosphorylation of PKC isozymes α, δ, θ in AGS cells, which was accompanied by the phosphorylation of PKC substrates, including PKCμ and myristoylated alanine-rich C kinase substrate (MARCKS), in a CagA-independent manner. Phospholipase C, phosphatidylinositol 3-kinase and Ca 2+ were crucial for PKC activation on infection; inhibition of PKC diminished AP-1 induction and, subsequently, MMP-1 expression. Invasion assays confirmed PKC involvement in H pylori -induced MMP-1 secretion. In addition, analysis of biopsies from human gastric mucosa showed increased phosphorylation of PKC in active H pylori gastritis and gastric adenocarcinoma. Conclusion The targeting of certain PKC isozymes might represent a suitable strategy to interfere with the MMP-1-dependent remodelling of infected tissue and to overcome the invasive behaviour of gastric cancer cells. |
| تدمد: | 1468-3288 0017-5749 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2efc8ab1e9e4691472fa7c7df3b5531Test https://doi.org/10.1136/gutjnl-2012-302103Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e2efc8ab1e9e4691472fa7c7df3b5531 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14683288 00175749 |
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