title: Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response.
abstract: 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.
authors.affiliation: Department of Digestive and Life-style related Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iwashita
authors.forename: Toshio
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ropeleski
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; C486114:Hspb1 protein, rat; D011073:Polyamines; D014157:Transcription Factors; D005973:Glutamine; D000518:Eflornithine