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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-3-31
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pubmed:abstractText |
Uroguanylin (UGN) is a peptide hormone that binds to and activates the intestinal epithelial cell (IEC) transmembrane receptor guanylate cyclase C (GC-C), which in turn increases intracellular cGMP. Gene targeting of murine UGN or GC-C results in significantly lower levels of cGMP in IECs. On the basis of effects of cGMP in nonintestinal systems, we hypothesized that loss of GC-C activation would increase intestinal epithelial apoptosis following radiation-induced injury. We first compared apoptosis from the proximal jejunum of C57BL/6 wild-type (WT) and GC-C knockout (KO) mice 3 h after they received 5 Gy of gamma-irradiation. We then investigated whether supplementation via intraperitoneal injection of 1 mM 8BrcGMP would mitigate radiation-induced apoptosis in these experimental animals. Identical experiments were performed in BALB/c UGN WT and KO mice. Apoptosis was assessed by quantitating morphological indications of cell death, terminal dUTP nick-end labeling, and cleaved caspase 3 immunohistochemistry. Both UGN KO and GC-C KO mice were more susceptible than their WT littermates in this in vivo model of apoptotic injury. Furthermore, cGMP supplementation in both GC-C and UGN KO animals ameliorated radiation-induced apoptosis. Neither WT strain demonstrated significant alteration in apoptotic susceptibility as a result of cGMP supplementation before radiation injury. These in vivo findings demonstrate increased radiosensitivity of IECs in UGN and GC-C KO mice and a role for cGMP as a primary downstream mediator of GC-C activation in the protection of these IECs from radiation-induced apoptosis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-10644554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-10735533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-10922987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11016642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11034578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11434904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11438734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11842009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11926897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-11947902,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-1394796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-14561709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-14614039,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-15108222,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-15860639,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-16288207,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19221018-9888876
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G740-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19221018-Animals,
pubmed-meshheading:19221018-Apoptosis,
pubmed-meshheading:19221018-Cyclic GMP,
pubmed-meshheading:19221018-Epithelial Cells,
pubmed-meshheading:19221018-Female,
pubmed-meshheading:19221018-Gamma Rays,
pubmed-meshheading:19221018-Guanylate Cyclase,
pubmed-meshheading:19221018-Immunohistochemistry,
pubmed-meshheading:19221018-In Situ Nick-End Labeling,
pubmed-meshheading:19221018-Intestinal Mucosa,
pubmed-meshheading:19221018-Male,
pubmed-meshheading:19221018-Mice,
pubmed-meshheading:19221018-Mice, Inbred BALB C,
pubmed-meshheading:19221018-Mice, Inbred C57BL,
pubmed-meshheading:19221018-Mice, Knockout,
pubmed-meshheading:19221018-Natriuretic Peptides,
pubmed-meshheading:19221018-Receptors, Guanylate Cyclase-Coupled,
pubmed-meshheading:19221018-Receptors, Peptide,
pubmed-meshheading:19221018-Signal Transduction,
pubmed-meshheading:19221018-Specific Pathogen-Free Organisms
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pubmed:year |
2009
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pubmed:articleTitle |
Activation of guanylate cyclase C signaling pathway protects intestinal epithelial cells from acute radiation-induced apoptosis.
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pubmed:affiliation |
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, and University of Cincinnati, MLC 2010, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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