ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Loss of Protein Kinase D2 Activity Protects Against Bleomycin-Induced Dermal Fibrosis in Mice.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Protein kinase D: A therapeutic target in experimental alcoholic pancreatitis.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.EMBO molecular medicine · 2021Article
- Pancreas-specific deletion of protein kinase D attenuates inflammation, necrosis, and severity of acute pancreatitis.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- Do Animal Models of Acute Pancreatitis Reproduce Human Disease?Cellular and molecular gastroenterology and hepatology · 2017Review
- Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis.Frontiers in physiology · 2017Article
- Mitochondrial and Oxidative Stress-Mediated Activation of Protein Kinase D1 and Its Importance in Pancreatic Cancer.Frontiers in oncology · 2017Review
- PKD signaling and pancreatitis.Journal of gastroenterology · 2016Review
- Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia.Nature communications · 2015Article
- Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Novel mechanism of cytokine-induced disruption of epithelial barriers: Janus kinase and protein kinase D-dependent downregulation of junction protein expression.Tissue barriers · 2013Article
- Article
- Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer.Gastroenterology · 2013Review
- Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Pathogenic mechanisms of acute pancreatitis.Current opinion in gastroenterology · 2012Review
- Protein kinase d regulates cell death pathways in experimental pancreatitis.Frontiers in physiology · 2012Article
- Molecular mechanisms of pancreatic injury.Current opinion in gastroenterology · 2011Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.
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