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Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells.

Publication ,  Journal Article
Niederlechner, S; Baird, C; Petrie, B; Wischmeyer, E; Wischmeyer, PE
Published in: Am J Physiol Gastrointest Liver Physiol
March 1, 2013

Epidermal growth factor receptor (EGFR) expression and signaling can induce cellular protection after intestinal inflammation. L-Glutamine (GLN) is known to prevent apoptosis after intestinal injury by activating MAPK and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. However, the role of EGFR expression and signaling in GLN-mediated cellular protection in intestinal epithelial-6 (IEC-6) cells after heat stress (HS) is unknown. To address the role of EGFR in GLN-mediated protection, IEC-6 cells were treated with GLN in the presence or absence of EGFR small interfering RNA, the EGFR tyrosine kinase inhibitor AG1478, the ERK1/2 inhibitor PD98059, the p38MAPK inhibitor SB203580, or the PI3-K/Akt inhibitor LY294002 under basal and HS conditions. GLN-mediated cell survival was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Phosphorylated and/or total levels of EGFR, cleaved caspase-3, poly(ADP-ribose) polymerase-1, ERK1/2, p38MAPK, and Akt were assessed by Western blotting. We showed that HS induced a decrease in total, cytoplasmic, and nuclear EGFR levels in IEC-6 cells, which was prevented by GLN supplementation, leading to attenuated apoptosis via EGFR small interfering RNA. Furthermore, the protective effect of GLN was lessened by AG1478, PD98059, and LY294002 but was not affected by SB203580. AG1478 attenuated GLN-mediated increases in ERK1/2 and decreases in p38MAPK phosphorylation. However, AG1478 had no effect on GLN-mediated augmentations in Akt phosphorylation. In summary, EGFR expression was important in the protective mechanism of GLN, as well as GLN-mediated activation of EGFR tyrosine kinase activity. GLN-mediated EGFR signaling activated ERK1/2 and decreased p38MAPK signaling. However, GLN-mediated Akt phosphorylation after HS seems to be independent of EGFR signaling.

Duke Scholars

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

March 1, 2013

Volume

304

Issue

5

Start / End Page

G543 / G552

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Signal Transduction
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • Intestines
  • Humans
  • Heat Stress Disorders
 

Citation

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ICMJE
MLA
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Niederlechner, S., Baird, C., Petrie, B., Wischmeyer, E., & Wischmeyer, P. E. (2013). Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells. Am J Physiol Gastrointest Liver Physiol, 304(5), G543–G552. https://doi.org/10.1152/ajpgi.00418.2012
Niederlechner, Stefanie, Christine Baird, Benjamin Petrie, Erhard Wischmeyer, and Paul E. Wischmeyer. “Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells.Am J Physiol Gastrointest Liver Physiol 304, no. 5 (March 1, 2013): G543–52. https://doi.org/10.1152/ajpgi.00418.2012.
Niederlechner S, Baird C, Petrie B, Wischmeyer E, Wischmeyer PE. Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells. Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G543–52.
Niederlechner, Stefanie, et al. “Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells.Am J Physiol Gastrointest Liver Physiol, vol. 304, no. 5, Mar. 2013, pp. G543–52. Pubmed, doi:10.1152/ajpgi.00418.2012.
Niederlechner S, Baird C, Petrie B, Wischmeyer E, Wischmeyer PE. Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells. Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G543–G552.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

March 1, 2013

Volume

304

Issue

5

Start / End Page

G543 / G552

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Signal Transduction
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • Intestines
  • Humans
  • Heat Stress Disorders