Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides

Basson, Marc D.; Fu, Hong

doi:10.1016/0304-3835(95)04058-7

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…However, it has been suggested that forskolin likely acts through a cAMP-independent mechanism, since 8Br-cAMP does not reproduce these perturbations (Sapin et al, 1997). Nevertheless, it has been demonstrated that treatment of Caco-2 cells with 8Br-cAMP decreases dipeptidyl peptidase specific activity, suggesting that intracellular cAMP may negatively regulate intestinal epithelial cell differentiation (Basson and Fu, 1996). In addition, higher adenylate cyclase activity was observed in undifferentiated Fig.…”

Section: Discussionmentioning

confidence: 96%

Cyclic AMP‐dependent protein kinase A negatively modulates adherens junction integrity and differentiation of intestinal epithelial cells

Boucher

Laprise

Rivard

2004

Journal Cellular Physiology

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Section: Discussionmentioning

confidence: 96%

Cyclic AMP‐dependent protein kinase A negatively modulates adherens junction integrity and differentiation of intestinal epithelial cells

Boucher

Laprise

Rivard

2004

Journal Cellular Physiology

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“…Several possible mechanisms have been reported for the effects of cyclic nucleotides on cancer growth, including suppression of proliferation by cell cycle arrest in G 0 -G 1 in human hepatocellular carcinoma cells (Wang et al, 2005), induction of apoptosis in human colon adenocarcinoma cells (Shailubhai et al, 2000), and induction of cell differentiation in human Caco-2 intestinal epithelial cells (Basson and Hong, 1996). Our study revealed an interesting finding that inhibition by overexpression of the ␣1␤1 Cys105 sGC was more potent in the colony formation assay than that in the MTT assay.…”

Section: Discussionmentioning

confidence: 99%

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Zhu¹,

Li²,

Zheng³

et al. 2011

Mol Pharmacol

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The NO and cGMP signaling pathways are of broad physiological and pathological significance. We compared the NO/soluble guanylyl cyclase (sGC)/cGMP pathway in human glioma tissues and cell lines with that of healthy control samples and demonstrated that sGC expression is significantly lower in glioma preparations. Our analysis of GEO databases (National Cancer Institute) further revealed a statistically significant reduction of sGC transcript levels in human glioma specimens. On the other hand, the expression levels of particulate (membrane) guanylyl cyclases (pGC) and cGMP-specific phosphodiesterase (PDE) were intact in the glioma cells that we have tested. Pharmacologically manipulating endogenous cGMP generation in glioma cells through either stimulating pGC by ANP/BNP, or blocking PDE by 3-isobutyl-1-methylxanthine/ zaprinast caused significant inhibition of proliferation and colony formation of glioma cells. Genetically restoring sGC expression also correlated inversely with glioma cells growth. Orthotopic implantation of glioma cells transfected with an active mutant form of sGC (sGC␣1␤1 Cys105 ) in athymic mice increased the survival time by 4-fold over the control. Histological analysis of xenografts overexpressing ␣1␤1Cys105 sGC revealed changes in cellular architecture that resemble the morphology of normal cells. In addition, a decrease in angiogenesis contributed to glioma inhibition by sGC/cGMP therapy. Our study proposes the new concept that suppressed expression of sGC, a key enzyme in the NO/cGMP pathway, may be associated with an aggressive course of glioma. The sGC/ cGMP signaling-targeted therapy may be a favorable alternative to chemotherapy and radiotherapy for glioma and perhaps other tumors.

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“…Plexiglas rings in the center of the Flexwell plates (placed before seeding) addressed the nonuniformity of strain in the center of the wells, excluding this area and allowing study of cells placed only around the periphery of the wells where strain is more uniform. Previous studies have demonstrated that cells experience reproducible elongation and relaxation in parallel with the repetitive deforming membrane with this technique (9,33).…”

Section: Methodsmentioning

confidence: 99%

Strain-induced Proliferation Requires the Phosphatidylinositol 3-Kinase/AKT/Glycogen Synthase Kinase Pathway

Gayer

Chaturvedi

Wang

et al. 2009

Journal of Biological Chemistry

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The intestinal epithelium is repetitively deformed by shear, peristalsis, and villous motility. Such repetitive deformation stimulates the proliferation of intestinal epithelial cells on collagen or laminin substrates via ERK, but the upstream mediators of this effect are poorly understood. We hypothesized that the phosphatidylinositol 3-kinase (PI3K)/AKT cascade mediates this mitogenic effect. PI3K, AKT, and glycogen synthase kinase-3␤ (GSK-3␤) were phosphorylated by 10 cycles/min strain at an average 10% deformation, and pharmacologic blockade of these molecules or reduction by small interfering RNA (siRNA) prevented the mitogenic effect of strain in Caco-2 or IEC-6 intestinal epithelial cells. Strain MAPK activation required PI3K but not AKT. AKT isoform-specific siRNA transfection demonstrated that AKT2 but not AKT1 is required for GSK-3␤ phosphorylation and the strain mitogenic effect. Furthermore, overexpression of AKT1 or an AKT chimera including the PH domain and hinge region of AKT2 and the catalytic domain and C-tail of AKT1 prevented strain activation of GSK-3␤, but overexpression of AKT2 or a chimera including the PH domain and hinge region of AKT1 and the catalytic domain and C-tail of AKT2 did not. These data delineate a role for PI3K, AKT2, and GSK-3␤ in the mitogenic effect of strain. PI3K is required for both ERK and AKT2 activation, whereas AKT2 is sequentially required for GSK-3␤. Furthermore, AKT2 specificity requires its catalytic domain and tail region. Manipulating this pathway may prevent mucosal atrophy and maintain the mucosal barrier in conditions such as ileus, sepsis, and prolonged fasting when peristalsis and villous motility are decreased and the mucosal barrier fails.

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Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides

Cited by 15 publications

References 22 publications

Cyclic AMP‐dependent protein kinase A negatively modulates adherens junction integrity and differentiation of intestinal epithelial cells

Cyclic AMP‐dependent protein kinase A negatively modulates adherens junction integrity and differentiation of intestinal epithelial cells

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Strain-induced Proliferation Requires the Phosphatidylinositol 3-Kinase/AKT/Glycogen Synthase Kinase Pathway

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