Cargando…

Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts

A metabolic phenomenon known as the Warburg effect has been characterized in certain cancerous cells, embryonic stem cells, and other rapidly proliferative cell types. Previously, our attempts to induce a Warburg-like state pharmaceutically via CPI-613 and PS48 treatment did augment metabolite produ...

Descripción completa

Detalles Bibliográficos
Autores principales: Mordhorst, Bethany R., Kerns, Karl C., Schauflinger, Martin, Zigo, Michal, Murphy, Stephanie L., Ross, Renee M., Wells, Kevin D., Green, Jonathan A., Sutovsky, Peter, Prather, Randall S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603033/
https://www.ncbi.nlm.nih.gov/pubmed/31263141
http://dx.doi.org/10.1038/s41598-019-45850-4
_version_ 1783431439393488896
author Mordhorst, Bethany R.
Kerns, Karl C.
Schauflinger, Martin
Zigo, Michal
Murphy, Stephanie L.
Ross, Renee M.
Wells, Kevin D.
Green, Jonathan A.
Sutovsky, Peter
Prather, Randall S.
author_facet Mordhorst, Bethany R.
Kerns, Karl C.
Schauflinger, Martin
Zigo, Michal
Murphy, Stephanie L.
Ross, Renee M.
Wells, Kevin D.
Green, Jonathan A.
Sutovsky, Peter
Prather, Randall S.
author_sort Mordhorst, Bethany R.
collection PubMed
description A metabolic phenomenon known as the Warburg effect has been characterized in certain cancerous cells, embryonic stem cells, and other rapidly proliferative cell types. Previously, our attempts to induce a Warburg-like state pharmaceutically via CPI-613 and PS48 treatment did augment metabolite production and gene expression; however, this treatment demonstrated a Reverse Warburg effect phenotype observed in cancer-associated stroma. In the current study, we inquired whether the mitochondria were affected by the aforementioned pharmaceutical treatment as observed in cancerous stromal fibroblasts. While the pharmaceutical agents decreased mitochondrial membrane potential in porcine fetal fibroblasts, the number and size of mitochondria were similar, as was the overall cell size. Moreover, the fibroblasts that were treated with CPI-613 and PS48 for a week had increased numbers of large autolysosome vesicles. This coincided with increased intensity of LysoTracker staining in treated cells as observed by flow cytometry. Treated fibroblasts thus may utilize changes in metabolism and autophagy to mitigate the damage of treatment with pharmaceutical agents. These findings shed light on how these pharmaceutical agents interact and how treated cells augment metabolism to sustain viability.
format Online
Article
Text
id pubmed-6603033
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-66030332019-07-14 Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts Mordhorst, Bethany R. Kerns, Karl C. Schauflinger, Martin Zigo, Michal Murphy, Stephanie L. Ross, Renee M. Wells, Kevin D. Green, Jonathan A. Sutovsky, Peter Prather, Randall S. Sci Rep Article A metabolic phenomenon known as the Warburg effect has been characterized in certain cancerous cells, embryonic stem cells, and other rapidly proliferative cell types. Previously, our attempts to induce a Warburg-like state pharmaceutically via CPI-613 and PS48 treatment did augment metabolite production and gene expression; however, this treatment demonstrated a Reverse Warburg effect phenotype observed in cancer-associated stroma. In the current study, we inquired whether the mitochondria were affected by the aforementioned pharmaceutical treatment as observed in cancerous stromal fibroblasts. While the pharmaceutical agents decreased mitochondrial membrane potential in porcine fetal fibroblasts, the number and size of mitochondria were similar, as was the overall cell size. Moreover, the fibroblasts that were treated with CPI-613 and PS48 for a week had increased numbers of large autolysosome vesicles. This coincided with increased intensity of LysoTracker staining in treated cells as observed by flow cytometry. Treated fibroblasts thus may utilize changes in metabolism and autophagy to mitigate the damage of treatment with pharmaceutical agents. These findings shed light on how these pharmaceutical agents interact and how treated cells augment metabolism to sustain viability. Nature Publishing Group UK 2019-07-01 /pmc/articles/PMC6603033/ /pubmed/31263141 http://dx.doi.org/10.1038/s41598-019-45850-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mordhorst, Bethany R.
Kerns, Karl C.
Schauflinger, Martin
Zigo, Michal
Murphy, Stephanie L.
Ross, Renee M.
Wells, Kevin D.
Green, Jonathan A.
Sutovsky, Peter
Prather, Randall S.
Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title_full Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title_fullStr Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title_full_unstemmed Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title_short Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
title_sort pharmacologic treatment with cpi-613 and ps48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603033/
https://www.ncbi.nlm.nih.gov/pubmed/31263141
http://dx.doi.org/10.1038/s41598-019-45850-4
work_keys_str_mv AT mordhorstbethanyr pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT kernskarlc pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT schauflingermartin pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT zigomichal pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT murphystephaniel pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT rossreneem pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT wellskevind pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT greenjonathana pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT sutovskypeter pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts
AT pratherrandalls pharmacologictreatmentwithcpi613andps48decreasesmitochondrialmembranepotentialandincreasesquantityofautolysosomesinporcinefibroblasts