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Glutamine induces heat shock protein expression via O-glycosylation and phosphorylation of HSF-1 and Sp1.
BACKGROUND: Glutamine (GLN) improves outcome in experimental and clinical states of illness and injury. The authors hypothesized GLN-mediated enhancement of O-glycosylation and subsequent phosphorylation of key transcription factors in the HSP70 pathway would lead to increased HSP70 expression following experimental sepsis. METHODS: Mice underwent cecal ligation and puncture (CLP)-induced sepsis and were treated with GLN (0.75 g/kg) or a saline placebo 30 minutes after CLP. A separate group of mice was treated with mithramycin, an Sp1 inhibitor. Lung tissue was harvested at 1, 2, 6, and 24 hours after CLP and was analyzed for HSF-1 and Sp1 O-GlcNAc modification, alpha-p-threonine modification, and HSP70. RESULTS: GLN increased O-GlcNAc modification of HSF-1 and Sp1 at 1 and 2 hours after sepsis (P < .001 vs saline). Samples immunoprecipitated for Sp1 and probed for subsequent phosphorylation showed a significant increase in nuclear alpha-p-threonine-modified Sp1 at 2 and 6 hours after sepsis (P < .001 vs saline). GLN increased phosphorylated nuclear HSF-1 at 1 and 2 hours after CLP (P < .001). Finally, GLN treatment increased HSP70 4-fold (P < .01), but when treated with mithramycin, this increase was attenuated at 2, 6, and 24 hours (P < .001 vs no mithramycin treatment). CONCLUSIONS: These results indicate that GLN induces HSF-1 and Sp1, which is known to lead to their nuclear translocation. The molecular mechanism of GLN-mediated HSP70 expression appears to be dependent on O-GlcNAc pathway activation and subsequent O-glycosylation and phosphorylation of key transcription factors required for HSP70 induction.
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Related Subject Headings
- Sepsis
- Random Allocation
- Protein Synthesis Inhibitors
- Plicamycin
- Oxidative Phosphorylation
- Nutrition & Dietetics
- Mice, Inbred C57BL
- Mice
- Male
- Lung
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=0148-6071&client=dukeuniv)
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sepsis
- Random Allocation
- Protein Synthesis Inhibitors
- Plicamycin
- Oxidative Phosphorylation
- Nutrition & Dietetics
- Mice, Inbred C57BL
- Mice
- Male
- Lung