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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Saha, Sayanti Ramachandra, Subbaraya G. Basu, Nirmalya Visweswariah, Sandhya S. Khan, Imran |
| Description | Author Affiliation: Basu N ( From the Department of Molecular Reproduction, Development, and Genetics and.) |
| Abstract | Guanylyl cyclase C (GC-C) is expressed in intestinal epithelial cells and serves as the receptor for bacterial heat-stable enterotoxin (ST) peptides and the guanylin family of gastrointestinal hormones. Activation of GC-C elevates intracellular cGMP, which modulates intestinal fluid-ion homeostasis and differentiation of enterocytes along the crypt-villus axis. GC-C activity can regulate colonic cell proliferation by inducing cell cycle arrest, and mice lacking GC-C display increased cell proliferation in colonic crypts. Activation of GC-C by administration of ST to wild type, but not Gucy2c(-/-), mice resulted in a reduction in carcinogen-induced aberrant crypt foci formation. In p53-deficient human colorectal carcinoma cells, ST led to a transcriptional up-regulation of p21, the cell cycle inhibitor, via activation of the cGMP-responsive kinase PKGII and p38 MAPK. Prolonged treatment of human colonic carcinoma cells with ST led to nuclear accumulation of p21, resulting in cellular senescence and reduced tumorigenic potential. Our results, therefore, identify downstream effectors for GC-C that contribute to regulating intestinal cell proliferation. Thus, genomic responses to a bacterial toxin can influence intestinal neoplasia and senescence. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 1 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-01-03 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Aging Cell Proliferation Colon Metabolism Cyclin-Dependent Kinase Inhibitor P21 Receptors, Guanylate Cyclase-Coupled Receptors, Peptide Up-Regulation Animals Cell Line, Tumor Pathology Cyclic GMP-Dependent Protein Kinases Genetics Mice Mice, Knockout Tumor Suppressor Protein P53 Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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