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

Yuan, Jingzhen; Lugea, Aurelia; Zheng, Ling; Gukovsky, Ilya; Edderkaoui, Mouad; Rozengurt, Enrique; Pandol, Stephen J.

doi:10.1152/ajpgi.90452.2008

Cited by 50 publications

(71 citation statements)

References 61 publications

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“…NF-κB is one of several key signaling systems that mediate the production of proinflammatory signals in acute pancreatitis [36]. Our study confirmed that NF-κB activity in KCs is upregulated in rats with SAP, implying that NF-κB signaling of KCs is one of the events in pancreatitis.…”

Section: Discussionsupporting

confidence: 81%

Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Wei

Huang

et al. 2011

Inflammation

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This study was undertaken to clarify the effects of taurine on liver injury in rats with severe acute pancreatitis (SAP). Rats were randomly assigned to three groups: a sham operation (SO), a SAP (established by infusion of 5% taurocholate), and a SAP given taurine (Taur). At 12 and 24 h post-operation, taurine pretreatment significantly attenuated hepatic tissue injury induced by SAP, and concurrently, serum alanine aminotransferase, aspartate transaminase, and amylase levels were significantly reduced by taurine pretreatment. Compared with the SO group, the total and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) expression and nuclear factor-κB (NF-κB) activity of Kupffer cells (KCs) were significantly higher in the SAP group, but taurine pretreatment inhibited the total and phosphorylated p38 MAPK expression and NF-κB activity of KCs in the SAP group. The increase of tumor necrosis factor-α and interleukin-lβ in cultured supernate of the SAP rat-derived KCs was also significantly inhibited by taurine pretreatment. These results suggest that taurine pretreatment ameliorated liver injury in rats with SAP mainly by inhibiting phosphorylated p38 MAPK and NF-κB activity in KCs, which may play an important role in liver injury.

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Section: Discussionsupporting

confidence: 81%

Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Wei

Huang

et al. 2011

Inflammation

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“…1) In the in vitro model, isolated pancreatic acini recapitulate the initial responses (i.e., inappropriate intracellular activation of zymogens) in acute pancreatitis when treated with supraphysiological concentrations of Cer or muscarinic agonists (Carb), without the influence of inflammation, nerves, or decreased blood flow. 2) In the in vivo model, Cer hyperstimulation consistently causes mild-to-moderate pancreatitis responses, including inflammation and vascular injury (6,32,38).…”

Section: Discussionmentioning

confidence: 99%

Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses

Alexandre

Uduman

Minervini

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Clinical studies indicate that cigarette smoking increases the risk for developing acute pancreatitis. The nicotine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major cigarette smoke toxin. We hypothesized that NNK could sensitize to pancreatitis and examined its effects in isolated rat pancreatic acini and in vivo. In acini, 100 nM NNK caused three- and fivefold activation of trypsinogen and chymotrypsinogen, respectively, above control. Furthermore, NNK pretreatment in acini enhanced zymogen activation in a cerulein pancreatitis model. The long-term effects of NNK were examined in vivo after intraperitoneal injection of NNK (100 mg/kg body wt) three times weekly for 2 wk. NNK alone caused zymogen activation (6-fold for trypsinogen and 2-fold for chymotrypsinogen vs. control), vacuolization, pyknotic nuclei, and edema. This NNK pretreatment followed by treatment with cerulein (40 μg/kg) for 1 h to induce early pancreatitis responses enhanced trypsinogen and chymotrypsinogen activation, as well as other parameters of pancreatitis, compared with cerulein alone. Potential targets of NNK include nicotinic acetylcholine receptors and β-adrenergic receptors; mRNA for both receptor types was detected in acinar cell preparations. Studies with pharmacological inhibitors of these receptors indicate that NNK can mediate acinar cell responses through an nonneuronal α(7)-nicotinic acetylcholine receptor (α(7)-nAChR). These studies suggest that prolonged exposure to this tobacco toxin can cause pancreatitis and sensitize to disease. Therapies targeting NNK-mediated pathways may prove useful in treatment of smoking-related pancreatitis.

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“…PKD was shown to function downstream of PKCδ and PKCε in pancreatic acinar cells stimulated by CCK-8. Specifically, PKD was necessary for NF-κB activation induced by these GPCR agonists in pancreatic cells (111). These results identify PKD as a novel element in the signaling pathways mediating NF-κB activation in acute pancreatitis.…”

Section: Pkd Signaling In Disease: Inflammatory Responses Cardiac Hymentioning

confidence: 99%

Protein Kinase D Signaling: Multiple Biological Functions in Health and Disease

2011

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Protein kinase D (PKD) is an evolutionarily conserved protein kinase family with structural, enzymological, and regulatory properties different from the PKC family members. Signaling through PKD is induced by a remarkable number of stimuli, including G protein-coupled receptor agonists and polypeptide growth factors. PKD1, the most studied member of the family, is increasingly implicated in the regulation of a complex array of fundamental biological processes, including signal transduction, cell proliferation and differentiation, membrane trafficking, secretion, immune regulation, cardiac hypertrophy and contraction, angiogenesis and cancer. PKD mediates such diverse array of normal and abnormal biological functions via dynamic changes in its spatial and temporal localization, combined with its distinct substrate specificity. Studies on PKD thus far indicate a striking diversity of both its signal generation and distribution and its potential for complex regulatory interactions with multiple downstream pathways, often regulating the sub-cellular localization of its targets.

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

Abstract: Yuan J, Lugea A, Zheng L, Gukovsky I, Edderkaoui M, Rozengurt E, Pandol SJ. Protein kinase D1 mediates NF-B activation induced by cholecystokinin and cholinergic signaling in pancreatic acinar cells.

Cited by 50 publications

References 61 publications

Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses

Protein Kinase D Signaling: Multiple Biological Functions in Health and Disease

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