Tumor promoter-induced changes in the permeability of epithelial cell tight junctions

Ojakian, George K.

doi:10.1016/0092-8674(81)90274-9

Cited by 174 publications

(72 citation statements)

References 41 publications

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“…8D, panel 3). The addition of cycloheximide blocks protein synthesis (28) and, hence, delivery from the TGN and allows detection of only transcytosis from the basolateral membrane (Fig. 8D, panel 4).…”

Section: Fig 1 Steady State Distribution Of the Wild Type (Wt) Or Mmentioning

confidence: 99%

Use of the H,K-ATPase β Subunit to Identify Multiple Sorting Pathways for Plasma Membrane Delivery in Polarized Cells

Vagin

Turdikulova

Yakubov

et al. 2005

Journal of Biological Chemistry

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A dynamic equilibrium between multiple sorting pathways maintains polarized distribution of plasma membrane proteins in epithelia. To identify sorting pathways for plasma membrane delivery of the gastric H,K-ATPase ␤ subunit in polarized cells, the protein was expressed as a yellow fluorescent protein N-terminal construct in Madin-Darby canine kidney (MDCK) and LLC-PK1 cells. Confocal microscopy and surface-selective biotinylation showed that 80% of the surface amount of the ␤ subunit was present on the apical membrane in LLC-PK1 cells, but only 40% was present in MDCK cells. Nondenaturing gel electrophoresis of the isolated membranes showed that a significant fraction of the H,K-ATPase ␤ subunits associate with the endogenous Na,K-ATPase ␣ 1 subunits in MDCK but not in LLC-PK cells. Hence, co-sorting of the H,K-ATPase ␤ subunit with the Na,K-ATPase ␣ 1 subunit to the basolateral membrane in MDCK cells may determine the differential distribution of the ␤ subunit in these two cell types. The major fraction of unassociated monomeric H,K-ATPase ␤ subunits is detected in the apical membrane. Quantitative analysis showed that half of the apical pool of the ␤ subunit originates directly from the trans-Golgi network and the other half from transcytosis via the basolateral membrane in MDCK cells. A minor fraction of monomeric ␤ subunits detected in the basolateral membrane represents a transient pool of the protein that undergoes transcytosis to the apical membrane. Hence, the steady state distribution of the H,K-ATPase ␤ subunit in polarized cells depends on the balance between (a) direct sorting from the trans-Golgi network, (b) secondary associative sorting with a partner protein, and (c) transcytosis.

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Section: Fig 1 Steady State Distribution Of the Wild Type (Wt) Or Mmentioning

confidence: 99%

Use of the H,K-ATPase β Subunit to Identify Multiple Sorting Pathways for Plasma Membrane Delivery in Polarized Cells

Vagin

Turdikulova

Yakubov

et al. 2005

Journal of Biological Chemistry

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“…Activation leads to the translocation of the enzyme from the soluble to membrane-associated particulate component of the cell (Gainer, 1985;Huang and Huang, 1993;Stabel and Parker, 1991). Studies using specific PKC activators have shown that PKC activation is closely associated with the loss of epithelial barrier function (Gainer, 1985;Ojakian, 1981), increase in transendothelial permeability (Lynch et al, 1991), and inhibition of astroglia-induced endothelial differentiation (Laterra et al, 1992). PKC is presumably present in nearly all types of tissues (Nishizuka, 1986;Stabel and Parker, 1991); however, the forms and activities of PKC in mammalian choroid plexus to our knowledge have never been characterized.…”

mentioning

confidence: 99%

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Zhao

Slavkovich

Zheng

1998

Toxicology and Applied Pharmacology

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Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood-brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood-CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 μM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1-10 μM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 μg Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood-CSF barrier in vitro, but not in vivo.The mammalian blood-cerebrospinal fluid (CSF) barrier resides primarily in the choroid plexus and plays a pivotal role in regulating the chemical stability of the central nervous system (Johanson, 1995;Davson and Segal, 1996). Toxic metals, especially lead (Pb), have been known to accumulate in the choroid plexus (Friedheim et al., 1983;Manton et al., 1984;O'Tuama et al., 1976;Zheng et al., 1991;Zheng, 1996). Our recent work revealed that accumulation of Pb in the choroid plexus is associated with a significant reduction in CSF concentrations of transthyretin (TTR), a major thyroxine-carrying protein in brain (Zheng et al., 1996). We postulated that Pb accumulation in the choroid plexus might also alter key enzymes that are apparently targeted by cellular Pb toxicity, such as the protein kinase C (PKC).

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“…isoforms are involved in this process; for example, addition of the phorbol ester phorbol 12-myristate-13-acetate (PMA) has been shown to reduce cell-to-cell contacts in epithelial cells (1). This compound has been widely used to activate PK-C in cells because it is membrane-permeable and causes a maintained stimulation of most members of this extended family (cPK-C and nPK-C) (2,3).…”

mentioning

confidence: 99%

Protein Kinase C-α Activity Inversely Modulates Invasion and Growth of Intestinal Cells

Batlle¹,

Verdú²,

Domı́nguez³

et al. 1998

Journal of Biological Chemistry

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The phorbol ester phorbol 12-myristate 13-acetate induces remarkable phenotypic changes in intestinal HT-29 M6 cells; these changes consist of loss of homotypic adhesion and inactivation of E-cadherin. In parallel, cell growth is retarded. We have transfected HT-29 M6 cells with an activated form of the conventional protein kinase C␣ (cPK-C␣). Expression of this isoform induced the acquisition of a scattered phenotype, similar to that adopted by cells after addition of phorbol 12-myristate 13-acetate, with very low cell-to-cell aggregation and undetectable levels of functional E-cadherin. These cell clones were highly motile and rapidly invaded embryonic chick heart fragments. Furthermore, cells expressing activated-cPK-C␣ showed decreased proliferation in comparison to control clones. We have also studied how these two apparently antagonistic changes affect the tumorigenic ability of HT-29 M6 cells. When the different cell clones were xenografted into athymic mice, the effect on cell growth seemed to predominate. Expression of activated-cPK-C␣ significantly reduced the size of the tumors; the cells with the highest level of expression did not even form subcutaneous tumors. Besides their smaller size, the morphology of these tumors was clearly different from those originated by HT-29 M6 cells, and they could be defined as infiltrative on anatomo-pathological basis. These results indicate that cPK-C␣ controls both cell-to-cell adhesion and proliferation of intestinal cells.

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Tumor promoter-induced changes in the permeability of epithelial cell tight junctions

Cited by 174 publications

References 41 publications

Use of the H,K-ATPase β Subunit to Identify Multiple Sorting Pathways for Plasma Membrane Delivery in Polarized Cells

Use of the H,K-ATPase β Subunit to Identify Multiple Sorting Pathways for Plasma Membrane Delivery in Polarized Cells

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Protein Kinase C-α Activity Inversely Modulates Invasion and Growth of Intestinal Cells

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