Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion in Helicobacter pylori infection
Sokolova O, Vieth M, Naumann M (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 62
Pages Range: 358-367
Journal Issue: 3
DOI: 10.1136/gutjnl-2012-302103
Abstract
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 Ca2+ 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.
Involved external institutions
Germany (DE)How to cite
APA:
Sokolova, O., Vieth, M., & Naumann, M. (2013). Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion in Helicobacter pylori infection. Gut, 62(3), 358-367. https://doi.org/10.1136/gutjnl-2012-302103
MLA:
Sokolova, Olga, Michael Vieth, and Michael Naumann. "Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion in Helicobacter pylori infection." Gut 62.3 (2013): 358-367.
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