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The mechanism of L‐Glutamine‐mediated protection requires the activation of cell surface receptors
Author(s) -
Niederlechner Stefanie,
Baird Christine,
Wischmeyer Paul
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb571
Subject(s) - integrin , proto oncogene tyrosine protein kinase src , apoptosis , chemistry , signal transduction , receptor , western blot , microbiology and biotechnology , glutamine , biology , biochemistry , amino acid , gene
L‐Glutamine (GLN), integrin/Src and epidermal growth factor receptor (EGFR) pathway can induce cellular protection. Hypothesis GLN activates the O‐glycosylation pathway, HSF‐1 and HSP expression via cell swelling by the activation of integrin/Src and EGFR signaling to prevent apoptosis. Methods IEC‐6 cells treated with GLN (up to 20 mM), with or without the integrin inhibitor GRGDSP (50 μM), inactive control peptide GRGESP (50 μM), Src‐kinase inhibitor PP‐2 (75 μM), or EGFR inhibitor AG1478 (10 μM). Cell survival via MTS assay 24h post‐HS (44ºCx50min). O‐glycosylated proteins, HSF‐1, HSPs, Bax, cleaved caspase‐3 and PARP levels determined via Western blot, cell area size via fluorescence microscopy after non‐lethal HS (43ºCx45min). Results GRGDSP significantly attenuated GLN‐mediated increases in cell area size, HSF‐1 and O‐GlcNAc levels after HS (p< 0.05; n>3). GLN‐mediated increases in HSPs were decreased by GRGDSP and PP2 by 70%–100% after HS (p< 0.05; n=4). GRGDSP, PP2, and AG1478 attenuated GLN's protection by 70%–100% (p< 0.05; n=4). GRGDSP increased GLN‐mediated decreases in cleaved caspase‐3, cleaved PARP and Bax levels after HS, indicating that GLN lost its protection (p<0.05; n=3). GRGESP control peptide had no effect on GLN‐mediated protection pathways. Conclusion Integrin/Src and EGFR signaling seem to be vital components of GLN's protective mechanism. R01 GM078312