Protein kinase C mediates experimental colitis in the rat

Brown, James F.; Qing, Chun; Tepperman, Barry L.

doi:10.1016/s0016-5085(98)81439-x

Cited by 4 publications

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“…known for its oncogenic activity in colon epithelial cells [29,30], but the role of this kinase in intestinal epithelial cell differentiation is unclear. PKCe expression is upregulated in colon mucosa during experimental colitis (Brown et al, 1999); it also plays a role in the control of chloride secretion across epithelium, whose deregulation is involved in significant pathological events, such as secretory diarrhea or cystic fibrosis (Chow et al, 2000). Moreover, it has been reported that PKCe mediates enterocyte migration in sepsis (Bu et al, 2007) and regulates thrombin-induced migration and adhesion of HT29 cells (Heider et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…PKCe expression has been reported in colon mucosa (Jiang et al, 1995) and intestinal cells (Saxon et al, 1994) where it was found associated with intermediate filaments (cytokeratins) of the belt desmosome. Furthermore, the development of experimental colitis, by 2,4,6trinitrobenzenesulfonic acid treatment, increases PKCe expression in rat mucosa (Brown et al, 1999). Although PKCe is also known for its oncogenic activity in colon epithelial cells (Perletti et al, 1996;Perletti et al, 1998), the role of this kinase in intestinal epithelial cell differentiation is unclear: indeed, it has been reported that butyrate reduces the levels of PKCe in the colon cancer cell lines LIM1215 and Caco-2, but this effect is unlikely to be a consequence of the induction of differentiation (Rickard et al, 2000).…”

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confidence: 94%

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TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

Gobbi

Marcantonio

Micheloni

et al. 2011

Journal Cellular Physiology

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PKC isoenzymes play central roles in various cellular signalling pathways, participating in a variety of protein phosphorylation cascades that regulate/modulate cellular structure and gene expression. It has been firmly established that several isoforms of PKC have a role in the regulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) activity. Our interest in probing the role of the epsilon isoform of PKC in the colonic cell differentiation stems from the discovery that PKCε and TRAIL are involved in the differentiation of other cell types like hematopoietic stem cells. Although the role of PKCε and TRAIL in the gastrointestinal system is unclear, it has been observed that PKCε has oncogenic activity in colon epithelial cells (CEC), while TRAIL increases the death of intestinal epithelial cells during inflammation. Here we demonstrate a reciprocal expression of PKCε and TRAIL in human colon mucosa: CECs at the bottom of the colonic crypts show high levels of PKCε, being negative for TRAIL expression. On the contrary, luminal CECs are positive for TRAIL, while negative for PKCε. Indeed, TRAIL- and butyrate-induced differentiation of the human colorectal cancer cell line HT29 requires the decrease of PKCε expression, whose absence in turn increases cell sensitivity to TRAIL-induced apoptosis. Moreover, TRAIL preferentially promotes HT29 differentiation into goblet cells. Taken together, this data demonstrate that TRAIL and PKCε must be reciprocally regulated to ensure physiological CEC differentiation starting from the stem cell pool, and that the down-regulation of PKCε is however critical for the differentiation and apoptosis of cancer cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

Gobbi

Marcantonio

Micheloni

et al. 2011

Journal Cellular Physiology

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“…, 1992). Thus, altered PKC signalling could underlie the reduced K Ca 3.1 activity in the colon of mice treated with DSS (Brown et al. , 1999; Chang et al.…”

Section: Discussionmentioning

confidence: 99%

Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener

Hirota

McKay

2009

British J Pharmacology

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Background and purpose: Epithelial surface hydration is critical for proper gut function. However, colonic tissues from individuals with inflammatory bowel disease or animals with colitis are hyporesponsive to Cl -secretagogues. The Cl -secretory responses to the muscarinic receptor agonist bethanechol are virtually absent in colons of mice with dextran sodium sulphate (DSS)-induced colitis. Our aim was to define the mechanism underlying this cholinergic hyporesponsiveness.

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“…Tumour necrosis factor (TNF)‐ α is involved in the regulation of many processes including experimentally induced intestinal inflammation ( Garside et al , 1993 ; Kojouharoff et al , 1997 ; Neurath et al , 1997 ; Brown et al , 1999 ). Furthermore, TNF levels have been shown to be increased in colonic tissue taken from Crohn's disease patients ( Beil et al , 1995 ) and in mononuclear cells harvested from mice with experimentally induced intestinal inflammation ( Schmitz et al , 1999 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of selective PKC isoform activation and inhibition on TNF‐α‐induced injury and apoptosis in human intestinal epithelial cells

Chang

Tepperman

2003

British J Pharmacology

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1 We have investigated the effects of specific PKC isoforms in TNF-a mediated cellular damage using a human intestinal cell line (SCBN). 2 TNF-a treatment induced a decrease in the extent of intestinal cellular viability as determined by a formazan-based assay and an increase in the apoptotic index as assessed by immunohistology. These changes in cellular integrity were found to be related to the degradation of I-kBa, mobilization of NFkB and release of mitochondrial cytochrome c. 3 TNF-a treatment also induced the activation of selective PKC isoforms which were associated with the decrease in cellular viability and an increase of cellular apoptosis. 4 Nonselective PKC antagonists, such as GF109203X and Go¨6976 as well as isoform-selective PKCinhibiting peptides would reverse the cellular injury as well as reduce the degradation of I-kBa and mitochondrial cytochrome c release. These effects were most highly correlated with changes in PKCd and e primarily. 5 Intestinal cellular injury could be induced by treating cells with agonists selective for PKCd and e mainly. 6 In conclusion, this study has shown that TNF-a treatment can induce the activation of PKCd and e in the human intestinal cell line, SCBN, and this response is closely associated with an increase in cellular damage and apoptosis. PKCd and e primarily mediate the release of mitochondrial cytochrome c and degradation of I-kBa and hence mobilization of NF-kB, which are responsible for the pathway leading to cell injury.

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Protein kinase C mediates experimental colitis in the rat

Cited by 4 publications

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TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener

Effect of selective PKC isoform activation and inhibition on TNF‐α‐induced injury and apoptosis in human intestinal epithelial cells

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Protein kinase C mediates experimental colitis in the rat

Cited by 4 publications

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TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

TRAIL up‐regulation must be accompanied by a reciprocal PKCε down‐regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation

Loss of Ca2+‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca2+‐activated K+ channel opener

Effect of selective PKC isoform activation and inhibition on TNF‐α‐induced injury and apoptosis in human intestinal epithelial cells

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Loss of Ca²⁺‐mediated ion transport during colitis correlates with reduced ion transport responses to a Ca²⁺‐activated K⁺ channel opener