PKC- and - regulate NF- B activation induced by cholecystokinin and TNF- in pancreatic acinar cells

نویسندگان

  • Akihiko Satoh
  • Anna S. Gukovskaya
  • Jose M. Nieto
  • Jason H. Cheng
  • Ilya Gukovsky
  • Joseph R. Reeve
  • Tooru Shimosegawa
  • Stephen J. Pandol
چکیده

Akihiko Satoh, Anna S. Gukovskaya, Jose M. Nieto, Jason H. Cheng, Ilya Gukovsky, Joseph R. Reeve, Jr., Tooru Shimosegawa, and Stephen J. Pandol Research Center for Alcoholic Liver and Pancreatic Diseases, Veterans Affairs Greater Los Angeles Health Care System and University of California, Los Angeles, California 90073; and Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi 980-8574, Japan

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Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules.

BACKGROUND AND AIMS Supramaximal concentrations of cholecystokinin (CCK) or cerulein induce the intracellular activation of trypsinogen and the transcription factor NF-kappaB, a key regulator of inflammatory gene expression. Both events occur early in the development of an acute pancreatitis. The aim of this study was to examine the relationship between intracellular trypsinogen and NF-kappaB a...

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Protein kinase D1 mediates NF-kappaB activation induced by cholecystokinin and cholinergic signaling in pancreatic acinar cells.

The transcription factor NF-kappaB plays a critical role in inflammatory and cell death responses during acute pancreatitis. Previous studies in our laboratory demonstrated that protein kinase C (PKC) isoforms PKCdelta and epsilon are key regulators of NF-kappaB activation induced by cholecystokinin-8 (CCK-8), tumor necrosis factor-alpha, and ethanol. However, the downstream participants in reg...

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Involvement of myristoylated alanine-rich C kinase substrate phosphorylation and translocation in cholecystokinin-induced amylase release in rat pancreatic acini.

Cholecystokinin (CCK) is a gastrointestinal hormone that induces exocytotic amylase release in pancreatic acinar cells. The activation of protein kinase C (PKC) is involved in the CCK-induced pancreatic amylase release. Myristoylated alanine-rich C kinase substrate (MARCKS) is a ubiquitously expressed substrate of PKC. MARCKS has been implicated in membrane trafficking in several cell types. Th...

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A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

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, CRT...

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Ethanol differentially regulates NF-kappaB activation in pancreatic acinar cells through calcium and protein kinase C pathways.

Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-kappaB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca(2+)- and PKC-mediated pathways of CCK-induced NF-kappaB activ...

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تاریخ انتشار 2004