Cargando…
Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury
Enterohemorrhagic Escherichia coli produce ribotoxic Shiga toxins (Stx), which are responsible for kidney injury and development of hemolytic uremic syndrome. The endoplasmic reticulum (ER) stress response is hypothesized to induce apoptosis contributing to organ injury; however, this process has be...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303821/ https://www.ncbi.nlm.nih.gov/pubmed/25609181 http://dx.doi.org/10.3390/toxins7010170 |
_version_ | 1782353978386808832 |
---|---|
author | Parello, Caitlin S. L. Mayer, Chad L. Lee, Benjamin C. Motomochi, Amanda Kurosawa, Shinichiro Stearns-Kurosawa, Deborah J. |
author_facet | Parello, Caitlin S. L. Mayer, Chad L. Lee, Benjamin C. Motomochi, Amanda Kurosawa, Shinichiro Stearns-Kurosawa, Deborah J. |
author_sort | Parello, Caitlin S. L. |
collection | PubMed |
description | Enterohemorrhagic Escherichia coli produce ribotoxic Shiga toxins (Stx), which are responsible for kidney injury and development of hemolytic uremic syndrome. The endoplasmic reticulum (ER) stress response is hypothesized to induce apoptosis contributing to organ injury; however, this process has been described only in vitro. ER stress marker transcripts of spliced XBP1 (1.78-fold), HSP40 (4.45-fold) and CHOP (7.69-fold) were up-regulated early in kidneys of Stx2 challenged mice compared to saline controls. Anti-apoptotic Bcl2 decreased (−2.41-fold vs. saline) and pro-apoptotic DR5 increased (6.38-fold vs. saline) at later time points. Cytoprotective activated protein C (APC) reduced early CHOP expression (−3.3-fold vs. untreated), increased later Bcl2 expression (5.8-fold vs. untreated), and had early effects on survival but did not alter DR5 expression. Changes in kidney ER stress and apoptotic marker transcripts were observed in Stx2-producing C. rodentium challenged mice compared to mice infected with a non-toxigenic control strain. CHOP (4.14-fold) and DR5 (2.81-fold) were increased and Bcl2 (−1.65-fold) was decreased. APC reduced CHOP expression and increased Bcl2 expression, but did not alter mortality. These data indicate that Stx2 induces renal ER stress and apoptosis in murine models of Stx2-induced kidney injury, but decreasing these processes alone was not sufficient to alter survival outcome. |
format | Online Article Text |
id | pubmed-4303821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43038212015-02-02 Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury Parello, Caitlin S. L. Mayer, Chad L. Lee, Benjamin C. Motomochi, Amanda Kurosawa, Shinichiro Stearns-Kurosawa, Deborah J. Toxins (Basel) Article Enterohemorrhagic Escherichia coli produce ribotoxic Shiga toxins (Stx), which are responsible for kidney injury and development of hemolytic uremic syndrome. The endoplasmic reticulum (ER) stress response is hypothesized to induce apoptosis contributing to organ injury; however, this process has been described only in vitro. ER stress marker transcripts of spliced XBP1 (1.78-fold), HSP40 (4.45-fold) and CHOP (7.69-fold) were up-regulated early in kidneys of Stx2 challenged mice compared to saline controls. Anti-apoptotic Bcl2 decreased (−2.41-fold vs. saline) and pro-apoptotic DR5 increased (6.38-fold vs. saline) at later time points. Cytoprotective activated protein C (APC) reduced early CHOP expression (−3.3-fold vs. untreated), increased later Bcl2 expression (5.8-fold vs. untreated), and had early effects on survival but did not alter DR5 expression. Changes in kidney ER stress and apoptotic marker transcripts were observed in Stx2-producing C. rodentium challenged mice compared to mice infected with a non-toxigenic control strain. CHOP (4.14-fold) and DR5 (2.81-fold) were increased and Bcl2 (−1.65-fold) was decreased. APC reduced CHOP expression and increased Bcl2 expression, but did not alter mortality. These data indicate that Stx2 induces renal ER stress and apoptosis in murine models of Stx2-induced kidney injury, but decreasing these processes alone was not sufficient to alter survival outcome. MDPI 2015-01-20 /pmc/articles/PMC4303821/ /pubmed/25609181 http://dx.doi.org/10.3390/toxins7010170 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Parello, Caitlin S. L. Mayer, Chad L. Lee, Benjamin C. Motomochi, Amanda Kurosawa, Shinichiro Stearns-Kurosawa, Deborah J. Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title | Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title_full | Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title_fullStr | Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title_full_unstemmed | Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title_short | Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury |
title_sort | shiga toxin 2-induced endoplasmic reticulum stress is minimized by activated protein c but does not correlate with lethal kidney injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303821/ https://www.ncbi.nlm.nih.gov/pubmed/25609181 http://dx.doi.org/10.3390/toxins7010170 |
work_keys_str_mv | AT parellocaitlinsl shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury AT mayerchadl shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury AT leebenjaminc shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury AT motomochiamanda shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury AT kurosawashinichiro shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury AT stearnskurosawadeborahj shigatoxin2inducedendoplasmicreticulumstressisminimizedbyactivatedproteincbutdoesnotcorrelatewithlethalkidneyinjury |