Modulation of human Caco‐2 intestinal epithelial cell phenotype by protein kinase C inhibitors

Basson, Marc D.; Fu, Hong

doi:10.1006/cbir.1995.1045

Cited by 11 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After first light-activating the calphostin C as previously described (7,34), we pretreated serum-starved Caco-2 cells with 10 nM calphostin C for 3 h before initiation of cyclic strain. We have previously shown that calphostin C treatment in this manner ablates strainstimulated PKC activity (6,7,34).…”

Section: Methodsmentioning

confidence: 86%

Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells

Duzgun

Sumpio

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Rhythmic strain stimulates Caco-2 proliferation. We asked whether mitogen-activated protein kinase (MAPK) activation mediates strain mitogenicity and characterized upstream signals regulating MAPK. Caco-2 cells were subjected to strain on collagen I-precoated membranes or antibodies to integrin subunits. Twenty-four hours of cyclic strain increased cell numbers compared with static conditions. MAPK-extracellular signal-regulated kinase (ERK) kinase inhibition (20 microM PD-98059) blocked strain mitogenicity. p38 Inhibition (10 microM SB-202190) did not. Strain rapidly and time-dependently activated focal adhesion kinase (FAK), paxillin, ERK1 and 2, and p38 on collagen. c-Jun NH(2)-terminal kinase (JNK)1 and 2 exhibited delayed activation. Similar activation occurred when Caco-2 cells were subjected to strain on a substrate of functional antibody to the alpha2-, alpha3-, alpha6-, or beta1-integrin subunits but not on a substrate of functional antibody to the alpha5-subunit. FAK inhibition by FAK397 transfection blocked ERK2 and JNK1 activation by in vitro kinase assays, but pharmacological protein kinase C inhibition did not block ERK1 or 2 activation by strain. Strain-induced ERK signals mediate strain's mitogenic effects and may require integrins and FAK activation.

show abstract

Section: Methodsmentioning

confidence: 86%

Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells

Duzgun

Sumpio

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…However, some observations suggest that activation of PKC is associated with intestinal and/or colonic cell proliferation, whereas PKC inhibition and translocation of the PKA catalytic subunit in the nucleus are associated with Caco‐2 cell differentiation (Craven and De Rubertis, 1987; Pignata et al, 1994). Interestingly, staurosporine has been shown to have hormesis‐like stimulatory and inhibitory effects on dipeptidyl dipeptidase and alkaline phosphatase activities, respectively, two differentiation markers in Caco‐2 cells (Basson and Hong, 1995). In the same study, staurosporine also decreased cell proliferation but still stimulated dipeptidyl dipeptidase activity in the presence of DNA synthesis inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Cadmium‐induced hormetic effect in differentiated Caco‐2 cells: ERK and p38 activation without cell proliferation stimulation

Mantha

Jumarie

2010

Journal Cellular Physiology

View full text Add to dashboard Cite

Cadmium (Cd) is a toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium may in part protect against Cd toxicity but is also a target tissue. Using human enterocytic-like Caco-2 cells, we have previously shown differences in sensitivity to Cd according to the differentiation status. The present study focuses on Cd effects on differentiated cells. Concentration and time-dependent increases in MTT (3-[4,5-dimethyl-2-thiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) activity were observed in post-confluent cultures exclusively, with a twofold maximal stimulation in 21-day-old cells exposed to 10 microM Cd for 24 h. No concomitant increase in [methyl-(3)H] thymidine incorporation was noted and Cd did not modify cell distribution in the cell-cycle phases. However, Cd-induced increase in MTT activity was inhibited by cycloheximine as well as by inhibitors of ERK1/2 and p38, but not by that of JNK. Consistently, Cd increased the levels of ERK1/2 and p38 phosphorylation. Inhibition of Ras-GTP or PI3K enhanced the stimulatory effect of Cd, whereas mTOR inhibition had no effect. Inhibition of G protein-phospholipase and PKC decreased MTT stimulation. These results show a hormesis-like stimulation of Cd on MTT activity in differentiated intestinal cells exclusively. This effect is not related to cell proliferation but more likely to increased protein synthesis which involves ERK1/2 and p38 cascades and possibly PLC-beta signaling pathways. Because growth-related differentiation of intestinal cells is linked to the selective and sequential activation of MAPKs, the impacts that these Cd-induced perturbations in signaling pathways may have on intestinal functions clearly deserve to be investigated.

show abstract

“…Nucleolin is a nuclear target protein for cyclic AMP and protein kinase C. Cyclic AMPdependent protein kinase influences the phosphorylation of nucleolin. According to Basson and Hong (1995), protein kinase C may regulate intestinal epithelial differentiation. Activation of Ca 2+ -dependent protein kinase C can cause a reduction in proliferation, while increasing apoptosis and differentiation in CaCo-2 cells (Chen et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Morphometry of nuclear and nucleolar structures in a CaCo‐2 cell line

Karalyan

Djaghatspanyan²,

Gasparyan

et al. 2004

Cell Biology International

View full text Add to dashboard Cite

The number of the nucleoli in a CaCo-2 cell nucleus does not generally depend on the quantity of DNA in the nucleus, but nucleolar DNA content is directly proportional to total nuclear DNA. However, in multinucleolar cells (three or more nucleoli), the nucleolar DNA content increases after 96 h incubation in culture without concomitant quantitative changes in nuclear DNA. The percentage of multinucleolar cells and the average number of nucleoli per nucleus increase with increasing incubation time. After 72 and 96 h in culture, multinucleolar cells show distinctive morphologies. The ratio of the sum of nucleolar perimeters to the nuclear perimeter increases linearly when the number of nucleoli in a nucleus increases, but there is no concomitant increase in total nucleolar area or DNA content, except in the 72 and 96 h populations. When the number of nucleoli in CaCo-2 cells increases after 48 and 60 h in culture, the amount of DNA per nucleolus decreases.

show abstract

Modulation of human Caco‐2 intestinal epithelial cell phenotype by protein kinase C inhibitors

Cited by 11 publications

References 12 publications

Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells

Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells

Cadmium‐induced hormetic effect in differentiated Caco‐2 cells: ERK and p38 activation without cell proliferation stimulation

Morphometry of nuclear and nucleolar structures in a CaCo‐2 cell line

Contact Info

Product

Resources

About