Skip to main content
Article thumbnail
Location of Repository

Activation of guanylate cyclase C signaling pathway protects intestinal epithelial cells from acute radiation-induced apoptosis

By M. P. Garin-Laflam, K. A. Steinbrecher, J. A. Rudolph, J. Mao and M. B. Cohen

Abstract

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 γ-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

Topics: Mucosal Biology
Publisher: American Physiological Society
OAI identifier: oai:pubmedcentral.nih.gov:2670662
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.