Document Detail


Polyamine depletion inhibits irradiation-induced apoptosis in intestinal epithelia.
MedLine Citation:
PMID:  15860639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our group has previously shown that polyamine depletion delays apoptosis in rat intestinal epithelial (IEC-6) cells (Ray RM, Viar MJ, Yuan Q, and Johnson LR, Am J Physiol Cell Physiol 278: C480-C489, 2000). Here, we demonstrate that polyamine depletion inhibits gamma-irradiation-induced apoptosis in vitro and in vivo. Pretreatment of IEC-6 cells with 5 mM alpha-difluoromethylornithine (DFMO) for 4 days significantly reduced radiation-induced caspase-3 activity and DNA fragmentation. This protective effect was prevented by the addition of 10 muM exogenous putrescine. Radiation exposure to mice resulted in a high frequency of apoptosis over cells positioned fourth to seventh in crypt-villus units. Pretreatment of mice with 2% DFMO in drinking water significantly reduced apoptotic cells from approximately 2.75 to 1.61 per crypt-villus unit, accompanied by significant decreases in caspase-3 levels. Further examination showed that DFMO pretreatment inhibited the radiation-induced increase in the proapoptotic protein Bax. Moreover, DFMO pretreatment significantly enhanced the intestinal crypt survival rate by 2.1-fold subsequent to radiation and ameliorated mucosal structural damage. We conclude that polyamine depletion by DFMO inhibits gamma-irradiation-induced apoptosis of intestinal epithelial cells both in vitro and in vivo through inhibition of Bax and caspase-3 activity, which leads to attenuation of radiation-inflicted intestinal injury. These data indicate that DFMO may be therapeutically useful to counteract the gastrointestinal toxicity caused by chemoradiotherapy. This is the first demonstration that polyamines are required for apoptosis in vivo.
Authors:
Wenlin Deng; Mary Jane Viar; Leonard R Johnson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-04-28
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  289     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-11     Completed Date:  2005-09-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G599-606     Citation Subset:  IM    
Affiliation:
Dept. of Physiology, Univ. of Tennessee Health Sciences Center, 894 Union Ave., Memphis, TN 38163, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Eflornithine / pharmacology
Enzyme Inhibitors / pharmacology*
Gamma Rays / adverse effects*
Intestinal Mucosa / cytology*,  pathology*
Male
Mice
Mice, Inbred C57BL
Polyamines / metabolism*
Radiation Injuries / physiopathology,  prevention & control
Radiation-Protective Agents / pharmacology
Grant Support
ID/Acronym/Agency:
DK-16505/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Polyamines; 0/Radiation-Protective Agents; 70052-12-9/Eflornithine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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