| Caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis: protective role of the nitric oxide signaling module. | |
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MedLine Citation:
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PMID: 15015762 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hydrophobic bile acids such as deoxycholate are known tumor promoters in the gastrointestinal tract. We have previously shown that deoxycholate induces apoptosis in colon epithelial cells and that these cells can be made resistant to deoxycholate-induced apoptosis. We now show that the nitric oxide synthase/nitric oxide/guanylate cyclase/cyclic guanosine monophosphate/cGMP-activated protein kinase (NOS/NO/GC/cGMP/PKG) signaling module contributes, in part, to the observed resistance of the cultured DOC-resistant colon epithelial cells (HCT-116R) using pharmacological inhibitors/antagonists (NS2028, Rp-8pCPT-cGMP, KT5823) of members of this signaling module. A novel finding from this study is the caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis of deoxycholate-sensitive HCT-116SA cells and the absence of guanylate cyclase alpha 1 cleavage in deoxycholate-treated HCT-116R resistant cells using Western blot analyses. This cleavage was specific to caspases as lysosomal, proteasomal, serine protease, cathepsin and calpain inhibitors failed to prevent the cleavage, whereas a general caspase inhibitor and a specific caspase-6 inhibitor did prevent guanylate cyclase alpha 1 cleavage. |
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Authors:
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C M Payne; C N Waltmire; C Crowley; C L Crowley-Weber; K Dvorakova; H Bernstein; C Bernstein; H Holubec; H Garewal |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cell biology and toxicology Volume: 19 ISSN: 0742-2091 ISO Abbreviation: Cell Biol. Toxicol. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2004-03-12 Completed Date: 2004-11-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8506639 Medline TA: Cell Biol Toxicol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 373-92 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA. cpayne@u.arizona.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Caspase 6 Caspases / metabolism* Colonic Neoplasms / enzymology* Cyclic GMP / metabolism Deoxycholic Acid / pharmacology* Enzyme Inhibitors / pharmacology Epithelial Cells / enzymology* Guanylate Cyclase / metabolism* Humans Nitric Oxide Donors / pharmacology Nitric Oxide Synthase / antagonists & inhibitors, metabolism Reactive Oxygen Species / metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/Reactive Oxygen Species; 7665-99-8/Cyclic GMP; 83-44-3/Deoxycholic Acid; EC 1.14.13.39/Nitric Oxide Synthase; EC 3.4.22.-/CASP6 protein, human; EC 3.4.22.-/Caspase 6; EC 3.4.22.-/Caspases; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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