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Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response.

Authors: Iwashita, Yuji  Sakiyama, Toshio  Musch, Mark W  Ropeleski, Mark J  Tsubouchi, Hirohito  Chang, Eugene B 
Citation: Iwashita Y, etal., Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G181-7. doi: 10.1152/ajpgi.00054.2011. Epub 2011 Apr 21.
Pubmed: (View Article at PubMed) PMID:21512157
DOI: Full-text: DOI:10.1152/ajpgi.00054.2011

Heat shock proteins (Hsps) are highly conserved proteins that play a role in cytoprotection and maintaining intestinal homeostasis. Glutamine is essential for the optimal induction of intestinal epithelial Hsp expression, but its mechanisms of action are incompletely understood. Glutamine is a substrate for polyamine synthesis and stimulates the activity of ornithine decarboxylase (ODC), a key enzyme for polyamine synthesis, in intestinal epithelial cells. Thus we investigated whether polyamines (putrescine, spermidine, or spermine) and their precursor ornithine mediate the induction of Hsp expression in IEC-18 rat intestinal epithelial cells. As previously observed, glutamine was required for heat stress induction of Hsp70 and Hsp25, although it had little effect under basal conditions. Under conditions of glutamine depletion, supplementation of ornithine or polyamines restored the heat-induced expression of Hsp70 and Hsp25. When ODC was inhibited by α-difluoromethylornithine (DFMO), an irreversible ODC inhibitor, the heat stress induction of Hsp70 and Hsp25 was decreased significantly, even in the presence of glutamine. Ornithine, polyamines, and DFMO did not modify the nuclear localization of heat shock transcription factor 1 (HSF-1). However, DFMO dramatically reduced glutamine-dependent HSF-1 binding to an oligonucleotide with heat shock elements (HSE), which was increased by glutamine. In addition, exogenous polyamines recovered the DNA-binding activity. These results indicate that polyamines play a critical role in the glutamine-dependent induction of the intestinal epithelial heat shock response through facilitation of HSF-1 binding to HSE.

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CRRD Object Information
CRRD ID: 10402944
Created: 2015-11-03
Species: All species
Last Modified: 2017-01-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.