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P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury

BACKGROUND: Glutamine appears to mediate protection against gut injury via multiple pathways. These include fibronectin-integrin, PI3-K/MAPK pathways, and activation of heat shock protein (HSP) response. We hypothesize there may be a relationship between these pathways mediating glutamine’s protecti...

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Autores principales: Niederlechner, Stefanie, Baird, Christine, Wischmeyer, Paul E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691833/
https://www.ncbi.nlm.nih.gov/pubmed/24499047
http://dx.doi.org/10.1186/1475-2891-12-88
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author Niederlechner, Stefanie
Baird, Christine
Wischmeyer, Paul E
author_facet Niederlechner, Stefanie
Baird, Christine
Wischmeyer, Paul E
author_sort Niederlechner, Stefanie
collection PubMed
description BACKGROUND: Glutamine appears to mediate protection against gut injury via multiple pathways. These include fibronectin-integrin, PI3-K/MAPK pathways, and activation of heat shock protein (HSP) response. We hypothesize there may be a relationship between these pathways mediating glutamine’s protection in intestinal epithelial-6 cells after heat stress. We assessed whether p38MAPK and PI3-K/Akt signaling are involved in glutamine’s cytoprotective mechanism and the role they play in glutamine-mediated protection in conjunction with fibronectin-integrin osmosignaling after hyperthermia. METHODS: Intestinal epithelial cells were treated for 15 min with glutamine, with/without the fibronectin-integrin interaction inhibitor GRGDSP, inactive control peptide GRGESP, p38MAPK inhibitor SB203580, or PI3-K/Akt inhibitor LY294002 under basal (37°C) and stressed (43°C or 44°C) conditions. Cell survival was measured via MTS assay 24 h post-heat stress (44°C × 50 min). Total p38MAPK, [T(P)(180)/Y(P)(182)]p38MAPK, total Akt, [S(P)(473)]Akt, HSP70, FN, and caspase-3 levels were determined via Western blot after non-lethal HS (43°C × 50 min). Additionally, HSP70 levels were assessed via Western blot and ELISA. RESULTS: We were able to show that GRGDSP and LY294002 attenuated glutamine’s protective effect. However, SB203580 increased cell survival after heat stress. LY294002 attenuated glutamine-mediated increases in fibronectin and in HSP70 expression after hyperthermia. GRGDSP increased glutamine-mediated attenuations in p38MAPK phosphorylation, but had no effect on glutamine-mediated augmentations in Akt phosphorylation. CONCLUSIONS: These data suggest that glutamine is protective after heat stress by activating PI3-K/Akt signaling preventing fibronectin-integrin expression and increasing HSP70 expression. Furthermore, dephosphorylation of p38MAPK after heat stress plays an important role in glutamine-mediated cellular protection. However, p38MAPK, but not PI3-K/Akt, signals downstream of glutamine-mediated fibronectin-integrin signaling after hyperthermia.
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spelling pubmed-36918332013-06-26 P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury Niederlechner, Stefanie Baird, Christine Wischmeyer, Paul E Nutr J Research BACKGROUND: Glutamine appears to mediate protection against gut injury via multiple pathways. These include fibronectin-integrin, PI3-K/MAPK pathways, and activation of heat shock protein (HSP) response. We hypothesize there may be a relationship between these pathways mediating glutamine’s protection in intestinal epithelial-6 cells after heat stress. We assessed whether p38MAPK and PI3-K/Akt signaling are involved in glutamine’s cytoprotective mechanism and the role they play in glutamine-mediated protection in conjunction with fibronectin-integrin osmosignaling after hyperthermia. METHODS: Intestinal epithelial cells were treated for 15 min with glutamine, with/without the fibronectin-integrin interaction inhibitor GRGDSP, inactive control peptide GRGESP, p38MAPK inhibitor SB203580, or PI3-K/Akt inhibitor LY294002 under basal (37°C) and stressed (43°C or 44°C) conditions. Cell survival was measured via MTS assay 24 h post-heat stress (44°C × 50 min). Total p38MAPK, [T(P)(180)/Y(P)(182)]p38MAPK, total Akt, [S(P)(473)]Akt, HSP70, FN, and caspase-3 levels were determined via Western blot after non-lethal HS (43°C × 50 min). Additionally, HSP70 levels were assessed via Western blot and ELISA. RESULTS: We were able to show that GRGDSP and LY294002 attenuated glutamine’s protective effect. However, SB203580 increased cell survival after heat stress. LY294002 attenuated glutamine-mediated increases in fibronectin and in HSP70 expression after hyperthermia. GRGDSP increased glutamine-mediated attenuations in p38MAPK phosphorylation, but had no effect on glutamine-mediated augmentations in Akt phosphorylation. CONCLUSIONS: These data suggest that glutamine is protective after heat stress by activating PI3-K/Akt signaling preventing fibronectin-integrin expression and increasing HSP70 expression. Furthermore, dephosphorylation of p38MAPK after heat stress plays an important role in glutamine-mediated cellular protection. However, p38MAPK, but not PI3-K/Akt, signals downstream of glutamine-mediated fibronectin-integrin signaling after hyperthermia. BioMed Central 2013-06-21 /pmc/articles/PMC3691833/ /pubmed/24499047 http://dx.doi.org/10.1186/1475-2891-12-88 Text en Copyright © 2013 Niederlechner et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Niederlechner, Stefanie
Baird, Christine
Wischmeyer, Paul E
P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title_full P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title_fullStr P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title_full_unstemmed P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title_short P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
title_sort p38map kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691833/
https://www.ncbi.nlm.nih.gov/pubmed/24499047
http://dx.doi.org/10.1186/1475-2891-12-88
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