Pharmacologic treatment with CPI-613 and PS48 decreases mitochondrial membrane potential and increases quantity of autolysosomes in porcine fibroblasts
| Autor: | Kevin D. Wells, Stephanie L. Murphy, Peter Sutovsky, Jonathan A. Green, Bethany R. Mordhorst, Martin Schauflinger, Karl Kerns, Michal Zigo, Randall S. Prather, Renee M. Ross |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Swine Autolysosome lcsh:Medicine Sulfides Mitochondrion Article Flow cytometry 03 medical and health sciences 0302 clinical medicine Stroma Macroautophagy Autophagy medicine Animals Pentanoic Acids lcsh:Science Membrane Potential Mitochondrial Multidisciplinary medicine.diagnostic_test Chemistry lcsh:R Energy metabolism Fibroblasts Warburg effect Embryonic stem cell Mitochondria 3. Good health Cell biology Microscopy Electron 030104 developmental biology lcsh:Q Caprylates Lysosomes 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-45850-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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